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Sustainable Lactic Acid Production from Lignocellulosic Biomass

Yalin Li, Sarang S. Bhagwat, Yoel R. Cortés-Peña, Dongwon Ki, Christopher V. Rao, Yong-Su Jin,
and Jeremy S. Guest*
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sı Supporting Information

ABSTRACT: Lignocellulosic biomass is a promising feedstock for

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sustainable biofuels and bioproducts. Among emerging bio-

products, lactic acid has attracted significant interest because of
its growing application in many industries (e.g., packaging,
medical, and pharmaceutical). In this study, BioSTEAMan
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open-source platformwas leveraged for the design, simulation,

and evaluation (via techno-economic analysis, TEA, and life cycle
assessment, LCA) of lignocellulosic lactic acid biorefineries. With a
minimum product selling price (MPSP) between $1.38 and 1.91
kg−1 (5th−95th percentiles, baseline at $1.57 kg−1), the biorefinery
was capable of producing market-competitive lactic acid (market price between $1.7 and 2.1 kg−1), and its performance could be
further enhanced (e.g., MPSP down to $1.09 kg−1, global warming potential of 2.79 kg CO2-eq·kg−1, and fossil energy consumption
of 31.7 MJ·kg−1) with advancements in key technological parameters (fermentation yield and separation process conversions) and
optimization in process operation. Sensitivity analyses focused on the fermentation unit (across titer, yield, and productivity; neutral
vs low-pH fermentation) and feedstock characteristics (carbohydrate content and price) were also included to quantify their impact
on the sustainability of the biorefinery. Overall, this research highlights the ability of agile TEA/LCA to screen promising biorefinery
designs, prioritize research needs, and establish a road map for the continued development of bioproducts and biofuels.
KEYWORDS: biorefinery design, techno-economic analysis (TEA), life cycle assessment (LCA), sensitivity, uncertainty, fermentation,
carbohydrate content, feedstock price

■ INTRODUCTION
It is critical for the society to displace the use of fossil fuels to
curb greenhouse gas emissions and combat climate change.1
Although petrochemicals only make up 16% of the oil-derived
products in the U.S., their total value is on par with petroleum
fuels (gasoline, diesel, and jet fuel), which represent 76% of oil-
derived products.2 To decarbonize the economy, a range of
technologies to produce petrochemical alternatives from first-
and second-generation (1G and 2G) feedstocks have been
proposed and some 1G bioproducts have been commercial-
ized. Because of their noncompetitiveness with food supply
and their potential to be provided at lower prices in large
quantities (e.g., sufficient to displace 30% of U.S. petroleum
consumption3) across a wide range of geographic locations,3,4
2G feedstocks have been found to reduce life cycle
environmental impacts of biofuels relative to 1G feedstocks,5,6
further motivating a shift in focus from 1G to 2G bioproducts.
Among the emerging bioproducts, lactic acid is one of the
most promising given its fast-growing market (projected
average annual growth rate >5% between 2018 and
20237−9). It has two optical enantiomersL-(+)-lactic acid
and D-(−)-lactic acidthat can be obtained by microbial
fermentation, but the L-form is the dominant commercial
product and will be the focus of this study.9,10 Lactic acid and
its salts (e.g., calcium lactate) have been widely used in food
and beverages (as an acidulant, in preservative and flavoring
agents, etc.); its polymers (e.g., polylactic acid) and esters (e.g.,
ethyl lactate) are increasingly used in packing, medical,
pharmaceutical, and food industries because of their
biodegradable and biocompatible properties.9 Currently, lactic
acid is predominantly (around 90%) produced from
fermentation of 1G sugars (e.g., corn starch and sugarcane
juice);4,9 if it can be made profitably and with lesser
environmental impacts, 2G (e.g., lignocellulose-derived) lactic
acid and its derivatives may expedite the phasing out of high-
volume, energy- and emission-intensive fossil-based plastics
and toxic solvents such as N-methyl-2-pyrrolidone (NMP),
toluene, acetone, and xylene.11
Despite recent achievements and ongoing efforts in
lignocellulose-derived lactic acid production (e.g., feedstock
supply12,13 and mutagenesis and metabolic engineering of
microorganisms10 ), published techno-economic analyses
Received: November 3, 2020
Revised: December 22, 2020
Published: January 12, 2021

© 2021 American Chemical Society https://dx.doi.org/10.1021/acssuschemeng.0c08055

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Figure 1. Simplified block flow diagram for conversion and separation processes. (A) Three conversion configurations were considered in this
study, and each of them was evaluated under (B) neutral and low-pH fermentation scenarios. Two separation configurations were designed to
accommodate the two fermentation scenarios (the two configurations were consistent for all three conversion configurations). In low-pH
fermentation, step 2 (dashed rectangle and associated chemical streams) was eliminated as lactic acid would not be converted to calcium lactate.
Acronyms in the figure denote solid/liquid separation (S/L separation) and wastewater treatment (WWT). Some streams are not included for
figure clarity; the process diagram flow in the system report includes the full set of details.27

(TEAs) and life cycle assessments (LCAs) of lactic acid
biorefineries have primarily focused on single or discrete sets of
assumptions without the flexibility to account for the variations
in feedstocks or to evaluate the implications of technological
advancements on biorefinery sustainability (in both economic
and environmental aspects) under uncertainty. Therefore, this
disconnect between the rapidly evolving state-of-technology
and static constrained approaches to TEA and LCA limits the
utility of system analyses, underscoring the need for more
productivity combinations) and to set targets for future
research. We further connected the design and performance
of the biorefinery to the feedstock supply chain by assessing
the implications of different feedstock carbohydrate contents
and prices. Altogether, conclusions from this study provide
critical insights into the prioritization of research and
development in multiple disciplines along the lactic acid
value chain, supporting the continued advancement toward a
sustainable bioeconomy.

robust methodologies to explore the potential for the
sustainable production of lignocellulose-derived lactic acid
under uncertainty.
The objective of this study was to characterize the potential
for sustainable lactic acid production from lignocellulosic
feedstocks. To this end, we leveraged BioSTEAM, an open-
source platform in Python,14−16 for the design, simulation, and
evaluation (via TEA and LCA) of biorefineries. Compared to
conventional process simulation tools (e.g., Aspen Plus), the
ability of BioSTEAM to automate system design and
simulation allows for agile and rapid uncertainty and sensitivity
analyses, enabling in-depth assessment of the variations in
biorefinery performance and identification of key factors
driving cost and environmental impacts.14−17 In particular,
we designed three different conversion (saccharification and
fermentation) configurations and two scenarios (neutral and
low-pH fermentation) to evaluate the system across the entire
fermentation design space (i.e., all possible titer, yield, and
■
METHODS
System Description. The biorefinery includes three inside-
battery-limit processes (pretreatment, conversion, and separation)
and two outside-battery-limit processes (wastewater treatment and
facilities; Figure S1 in the Supporting Information). Incoming
lignocellulosic feedstocks (2000 metric tonnes per day as in Humbird
et al.,18 representing all feedstocks available within a 50 mile radius;
baseline composition of the feedstock was set to be the same as in
Humbird et al.18), which have been preprocessed to meet the quality
specifications (e.g., size, ash, and moisture19), are pretreated with
dilute sulfuric acid to depolymerize the majority of the hemicellulose
and a minor fraction of cellulose (i.e., glucan) into their respective
sugar oligomers and monomers. The pretreated slurry is then
conditioned and sent to the conversion process for saccharification
(enzymatic hydrolysis) of cellulose and fermentation of glucose and
xylose to L-(+)-lactic acid. Although emerging pretreatment
technologies such as ionic liquid20 and deacetylation and mechanical
refining21 can lead to higher solid loading (which is beneficial for

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Figure 2. Uncertainties (box and whisker plots) and breakdowns (stacked bar charts) of (A) minimum product selling price (MPSP), (B) 100-year
global warming potential (GWP100), and (C) fossil energy consumption (FEC). Whiskers, boxes, and the middle line represent 5th/95th, 25th/
75th, and 50th percentiles from 1000 Monte Carlo simulation, respectively. Diamonds and stacked bar charts report results for baseline values. In
panel (B), P and C for natural gas represent emissions associated with production and onsite combustion, respectively. Tabulated breakdown data
for capital and material costs, heating and cooling duties, electricity usage, GWP100, and FEC are available online.27

downstream processes), their current costs remain prohibitively
high22,23 and they were thus not considered in this study.
Three configurations for the conversion process were designed to
evaluate the biorefinery across the entire titer−yield fermentation
performance space (Figure 1A, described in the Supporting
Information): (configuration 1) dilution of the saccharified stream
with batch fermentation; (configuration 2) concentration of the
saccharified stream via multi-effect evaporation with batch fermenta-
tion; and (configuration 3) concentration of the saccharified stream
with continuous fermentation. Through a preliminary analysis, each of
these configurations was demonstrated to be the optimal choice for
the specific titer−yield combinations across the cost and environ-
mental impact metrics examined in this study (more details in the
Results and Discussion). Across the full titer−yield performance
space, these three configurations were evaluated under two scenarios:
a neutral fermentation scenario where common, neutrophilic strains
are used in fermentation and lime is added to neutralize the generated
lactic acid and prevent product inhibition (due to pH drop) and a
low-pH fermentation scenario where acid-resistant strains are used
and lime addition is eliminated. Key parameters (e.g., titer, yield, and
productivity) for the fermentation unit were selected based on
literature data that (i) used lignocellulosic feedstocks and (ii)
converted both glucose and xylose (i.e., realized cofermentation)
into lactic acid (Figure S2 and Table S3 in the Supporting
Information). Although diauxic utilizationwhere glucose and xylose
are used sequentially (as opposed to simultaneously)could occur,24
its effect would already be reflected in the data given that overall
fermentation parameters (e.g., yield calculated as the total amount of
produced lactic acid divided by the sum of glucose and xylose rather
than individual yield from glucose or xylose) were used.
After fermentation, the broth is directed to the separation process
(Figure 1B) for product recovery. In the neutral fermentation
scenario, sulfuric acid is added to convert calcium lactate into lactic
acid and gypsum (CaSO4), but this step is eliminated in the low-pH
fermentation scenario. The crude lactic acid stream is then purified by
esterification (lactic acid to ethyl lactate) and hydrolysis (ethyl lactate
to lactic acid) coupled with distillation and flash for light and heavy
impurity removal. The final product is 88% L-(+)-lactic acid (on
weight basis) with majority of the impurities being water and ethyl
lactate. Although alternative technologies (e.g., solvent extraction and
electrodialysis; more details in Section S1.2 in the Supporting
Information) have been considered for the separation process, the
sequential esterification−hydrolysis technology selected for this study
is the most mature one with successful industrial application at the
commercial scale.9,25,26
Wastewater streams are treated by anaerobic digestion (with
coproduction of biogas), aerobic digestion, a membrane bioreactor,
and reverse osmosis, and the treated water is reused in other
processes. Wastewater sludge is dewatered using a belt thickener and
centrifuge. Facilities in the biorefinery include a boiler (onsite heat
production), cooling tower (CT, cooling demand management), heat
exchanger network (heat integration to minimize utility demands),
process water center (water reuse management), and other auxiliary
units for storage, air distribution, and clean-in-place.
We executed the design, simulation, and evaluation of the
biorefinery using BioSTEAM,14,15 which enables rigorous mass and
energy flow tracking through the biorefinery. Influent and effluent
streams of each unit are automatically simulated using BioSTEAM to
determine mass and energy flows throughout the system, and these
streams are subsequently used with operating parameters and
equipment cost algorithms for unit design and cost calculation.
Process details (conversion, separation processes, and facilities) and
lists of major units in the biorefinery are included in the Supporting
Information. Baseline values of key parameters are included in Table
S5 in the Supporting Information. All Python scripts (including
biorefinery setup and system analyses) and a system report (including

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a process flow diagram, stream and cost tables, unit design
specifications, and utilities) for the baseline simulation are available
online.27
System Analyses under Uncertainty. We performed TEA for
the designed biorefinery using BioSTEAM’s discounted cash flow rate
of return analysis to calculate the minimum product selling price
(MPSP) of lactic acid to achieve a net present value of zero. The
biorefinery was modeled as an nth plant (i.e., a successful industry has
been established with mature technologies). Key construction (e.g.,
warehouse and site development), fixed operating (e.g., labor burden
and property insurance), and financial (e.g., depreciation and taxes)
parameters followed assumptions in previous studies18,22 and are
included in the Python script.27 All costs and prices shown are
presented in 2016 U.S. dollars.
We conducted LCA in Python using the simulated stream (input
chemicals and emissions) and utility inventories from BioSTEAM.
The system boundary of the LCA was set to the biorefinery fence line
and the functional unit was set to 1 kg of produced lactic acid (88%
on weight basis, the L-form) to be consistent with the TEA. Impact
characterization factors were collected from the literature and their
sources were noted in the script.27 To focus on the biorefinery, we
excluded impacts associated with the feedstock (highly sensitive to the
feedstock type and assumptions of land use change28,29) and wastes
(highly sensitive to end-of-life assumptions; e.g., gypsum as a
coproduct or waste30,31). Impacts resulting from infrastructure
construction were also excluded to be consistent with the U.S.
renewable fuel standard (RFS).32 Our presentation of environmental
impacts focused on two impact categories100-year global warming
potential (GWP100) and fossil energy consumption (FEC)which
were selected based on their prominence in the literature and their
relevance to policies and legislation.30,33
Uncertainty analysis was conducted for the baseline biorefinery
design (configuration 1 with the amount of dilution water in Figure
1A set to zero) for the neutral fermentation scenario using Monte
Carlo simulation with Latin hypercube sampling (1000 simulations)
and included 27 parameters. A full list of the evaluated parameters,
their uncertainty ranges, and literature references are provided in
Table S5 in the Supporting Information. We assigned triangular
distributions for parameters with strong literature support, and we
assigned uniform distributions for parameters for which literature
values were lacking (detailed description on the choice of the
distribution type and range is included in the Supporting
Information). The sensitivities of MPSP, GWP100, and FEC to all
uncertain inputs were determined via Spearman’s rank correlation
coefficients (Spearman’s ρ) using the Monte Carlo simulation data.
For select parameters which had large uncertainties and were likely to
have significant impacts on biorefinery performancethis included
fermentation titer, yield, productivity, and feedstock carbohydrate
content and pricewe performed separate analyses to characterize
the sustainability implications of uncertainty around these parameters.
All analysis results are available online.27
■
RESULTS AND DISCUSSION
Financial Viability under Uncertainty. The MPSP of
lactic acid was estimated to be $1.57 kg−1 (baseline) with a
range of $1.38−1.91 kg−1 [hereinafter, 5th−95th percentiles
are shown in brackets]. A total of 70% and >99% of the
simulated results were below the lower ($1.7 kg−1) and upper
range ($2.1 kg−1) of the market price, respectively, indicating
that the designed biorefinery was likely to be financially viable
(Figure 2A). Across the biorefinery, the boiler and the
separation process were the most capital-intensive components
(35% [33−37%] and 22% [20−25%] of the total capital cost,
respectively), while the wastewater treatment, conversion, and
pretreatment processes (in descending order) each accounted
for roughly 10% of the total capital cost. For material costs, the
boiler (32% [26−36%]) and the conversion process (30%
[24−33%]) were the largest contributors, which were followed
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pubs.acs.org/journal/ascecg Research Article
by feedstock cost (23% [20−27%]); the remaining system
accounted for much smaller shares (tabulated data available
online27). The high capital and operating costs associated with
the boiler came from the large heating demand of the system,
which in turn required a large boiler (hence high capital cost);
as the energy in the biogas and solid waste (lignin and
unconverted carbohydrates) was unable to satisfy the heating
demand, a substantial amount of natural gas (27% [21−31%]
of the annual material cost) was purchased to overcome the
energy deficit. Another noteworthy aspect is that 26% [20−
28%] of the annual material cost was associated with lactic acid
neutralization (to calcium lactate with lime during fermenta-
tion, 17% [12−18%]) and calcium lactate acidulation (back to
lactic acid with sulfuric acid in the separation process, 9% [8−
20%]), suggesting that the material cost (and thus the MPSP)
could be substantially reduced in the low-pH fermentation
scenario because of the elimination of these chemicals.
Examining the breakdown of heating and cooling demands,
the separation process was found to be the predominant utility
user with 93% [91−94%] of the total heating demand and 89%
[88−91%] of the total cooling demand. In particular, around
46% of demand for both utilities was associated with the first
flash unit (step 3 in Figure 1B), which was used to remove
water and volatile organics to concentrate the dilute lactic acid
solution. These results indicated that a higher lactic acid titer
after fermentation could lead to lower utility usage (because
less water would need to be removed) and lower material (less
natural gas for the boiler) and capital (smaller boiler and CT
units) costs, thus lowering the MPSP. Notably, by pairing
available hot and cold streams, the heat exchange network unit
offsets 11% [10−12%] and 15% [13−16%] of the overall
heating and cooling demand, respectively, with a negligible
(<1%) increase in capital cost (pinch diagram included in
Figure S3 in the Supporting Information). With regard to
electricity, consumption was more evenly distributed, but the
fact that the boiler and CT used nearly 40% of the total
electricity again suggested that heating and cooling utility-
related factors had sizeable impacts on the economics of the
biorefinery (electricity cost accounted for roughly 10% of the
annual operating cost).
At different internal rates of return (IRRs), the MPSP varied
from $1.19−1.69 kg−1 at 0% IRR and $2.18−3.07 kg−1 at 40%
IRR (5th−95th percentiles) and the median value crossed the
lower ($1.7 kg−1) and upper ($2.1 kg−1) market price at 14%
and 27% IRRs, respectively (Figure S4 in the Supporting
Information). These results fell within the range of MPSPs
reported in previous studies for lignocellulose-derived lactic
acid ($0.46−3 kg−1 at 8−31.1% IRR) with varying biorefinery
designs and assumptions (literature data and corresponding
assumptions shown in Figure S4).34−39 Generally, the studies
that reported the lowest MPSPs assumed (i) high solid loading
in pretreatment and conversion processes (>50% higher than
those assumed in this study) and (ii) cofermentation that
utilized both glucose and xylose. This variation in the MPSP
with solid loading and substrate utilization was consistent with
this study: higher solid loadings would lessen the utility
intensity of separations and save both operating and capital
costs, and cofermentation would substantially increase the
overall lactic acid yield (per kg of feedstock) compared to
utilizing glucose or xylose alone. In this study, cofermentation
and solid loadings of 30% (pretreatment) and 20%
(saccharification) were assumed, which had been experimen-
tally demonstrated (Figure S2 and Table S3 in the Supporting
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Figure 3. Spearman’s ρ values between input parameters and MPSP, GWP100, and FEC. EH represents enzymatic hydrolysis (i.e., saccharification),
EH solid loading represents the solid concentration during EH, enzyme loading represents the amount of enzyme added per gram of cellulose
during EH. TCI ratio represents total capital investment as a % of the value estimated by BioSTEAM, ES represents esterification, and HY
represents hydrolysis. Bullet points indicate the parameters that affect biorefinery mass and energy (M & E) flows, annual lactic acid production,
capital cost, and operating cost. A total of 27 parameters were selected for sensitivity analysis (full list, distributions, and ρ values included in Table
S5 in the Supporting Information) and only parameters with absolute values of ρ ≥ 0.1 for MPSP are shown here. Crossed circles indicate that
GWP100 or FEC were not appreciably (absolute value of ρ < 0.05) affected by the parameters. Parameters with absolute values of ρ ≥ 0.1 for
GWP100 or FEC are included in Figure S6 in the Supporting Information. The impact of changing each individual parameter to its minimum or
maximum value on MPSP, GWP100, and FEC is also included in Figure S6.

Information for cofermentation data; Tao et al.40 for solid
loading data; and Table S5 in the Supporting Information for
values used in simulations) and reflect the state of technology.
Environmental Impacts under Uncertainty. The base-
line GWP100 and FEC of lactic acid production were 5.92
[4.99−7.05] kg CO2-eq·kg−1 and 77.2 [62.9−93.3] MJ·kg−1,
respectively (Figure 2B,C). Similar to MPSP, GWP100 and
FEC were dominated by conversion- and separation-related
chemical inputs and emissions. In particular, 59% [53−63%] of
GWP100 and 72% [67−75%] of FEC were associated with the
natural gas used in the boiler. Thus, reducing the heating
demand was not only important for lowering the MPSP but
was also critical for limiting environmental impacts. Moreover,
the boiler and CT units were heavy electricity users (23% [21−
23%] and 16% [15−16%], respectively; the boiler used
electricity for pumping and flue gas desulfurization, etc.;
Figure 2A), and the electricity overall accounted for 13% [12−
16%] of GWP100 and 13% [12−15%] of FEC. Besides natural
gas and electricity, lime used in the fermentation unit was also
a notable contributor to GWP100 (15% [14−18%]) and FEC
(5% [4−5%]), indicating the potential environmental benefits
of employing acid-resistant strains for low-pH fermentation.
The remaining impacts were attributed to all other materials
used throughout the biorefinery, which were relatively small
(totaling 12% [10−14%] for GWP100 and 10% [9−13%] for
FEC) compared to those discussed above.
Compared to the GWP100 of 0.7−3.3 CO2-eq·kg−1 and FEC
of 24−56 MJ·kg−1 reported in the literature using similar
production routes from lignocellulosic feedstocks,30,41−43
results herein were relatively higher. This disparity is due to
the conservative assumptions used in this study, which were
based on experimental data. For example, in the fermentation
unit, lactic acid yields as high as 0.98 g·g−1 from glucose (for
1G and 2G lactic acid) and 0.95 g·g−1 from xylose, arabinose,
galactose, and mannose (for 2G lactic acid) have been used in
the published literature,30 which were much higher than the
0.76 g·g−1 (median value of collected experimental data) for
only glucose and xylose assumed in this study. Similarly, for the
esterification and hydrolysis units (steps 4 and 7 in Figure 1B)
1345
in the separation process, experimentally based models and
data44−46 were used to derive reaction conversions, which were
around 19% for the esterification unit and 80% for the
hydrolysis unit. However, much higher conversions (e.g., 88−
98.5% for esterification and 95−98.5% for hydrolysis33,41,42,47)
were used in previous studies. If similar optimistic assumptions
in fermentation (lactic acid yield of 0.95 g·g−1 from glucose
and xylose), esterification (90% conversion), and hydrolysis
(90% conversion) units were used, GWP100 and FEC would
decrease from 5.92 to 3.56 CO2-eq·kg−1 and 77.2 to 44.5 MJ·
kg−1, respectively, and MPSP would also decrease from the
baseline of $1.57 kg−1 to $1.02 kg−1 (Figure S5 in the
Supporting Information). Moreover, using renewable heating
sources (e.g., from an on-farm biogas plant48) or diverting a
portion of the biomass directly to the boiler49 could also
reduce environmental impacts. For example, with 25% of
natural gas from renewable sources and 25% of feedstocks
directly diverted to the boiler (values chosen for illustrative
purposes), GWP100 and FEC could be further reduced to 2.79
CO2-eq·kg−1 and 31.7 MJ·kg−1, respectively. Although this
change would increase MPSP slightly to $1.09 kg−1 (because
less feedstock would be available for lactic acid production),
this final price is still well below the commercial market price
range.
Drivers of Cost and Environmental Impacts. To
systematically assess the cost and environmental impact drivers
of the biorefinery, we conducted a sensitivity analysis using
Spearman’s rank correlation coefficients, where the absolute
value of Spearman’s ρ represents the strength of the rank
correlation and the symbol (+ or −) of ρ represents positive or
negative correlation.
MPSP was most sensitive (i.e., absolute value of Spearman’s
ρ ≥ 0.1) to 12 of the examined parameters, which affected
MPSP through mass and energy flows, annual lactic acid
production, and capital and/or operating costs (Figure 3 and
Table S5 in the Supporting Information). Of these 12
parameters, one set impacted MPSP through the production
of lactic acid either by affecting the available sugar substrate
(glucan to glucose conversion) or lactic acid fermentation
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Figure 4. (A,B) MPSP, (C,D) GWP100, and (E,F) FEC at different titer and yield combinations at baseline productivity (0.89 g·L−1·h−1) for neutral
[left panel; (A,C,E)] and low-pH [right panel; (B,D,F)] fermentation scenarios. For a given point on the figure, the x-axis value represents the yield
(same for glucose and xylose), the y-axis value represents the titer, and the color represents the value of MPSP, GWP100, or FEC (values at the same
titer−yield combination are from the same simulation). Although configuration 3 could be implemented across the space occupied by
configurations 1−3 and configuration 2 could be implemented in the space occupied by configurations 1−2, each configuration was optimal (lowest
MPSP, GWP100, and FEC) in the region defined in the legend. Three different configurations (configurations 1−3, legend) were designed to
simulate all potential titer−yield combinations. Detailed descriptions of the three configurations and results for different productivities are included
in the Supporting Information.

yield. A second set of these parameters, on the other hand,
impacted MPSP through the recovery of lactic acid and
included enzymatic hydrolysis (i.e., saccharification) solid
loading (determined the amount of water impurities to be
removed in the separation process), esterification conversion,
and hydrolysis conversion. Together, these two sets of
parameters affected the annual production of lactic acid (for
a fixed feedstock rate). Additionally, many of these parameters
also directly influenced total capital and operating costs
because of the large costs of the respective equipment,
materials, and utilities. Aside from these two sets of
parameters, boiler efficiency had substantial effects on the
energy flows through the biorefinery and thus MPSP (because
of the utility-driven nature of the total operating cost). The
remaining six parameters did not have significant impacts on
1346
the mass and energy flows of the biorefinery but affect MPSP
by impacting the capital or material costs.
With regard to environmental impacts, both GWP100 and
FEC were most sensitive to boiler efficiency, lactic acid
fermentation yield, enzymatic hydrolysis solid loading,
esterification conversion, and hydrolysis conversion (Figures
3 and S6B,C in the Supporting Information), which was
consistent with the utility-driven breakdown of these two
indicators (Figure 2B,C). Notably, although an increase in all
these parameters would lessen the energy intensity of the
biorefinery and thus reduce GWP100 and FEC, parameters
other than the boiler efficiency also indirectly affected GWP100
and FEC by increasing total annual lactic acid production
(thereby reducing the impacts and energy consumption per 1
kg of lactic acid, the functional unit of the LCA). Moreover,
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ACS Sustainable Chemistry & Engineering
the fact that Spearman’s ρ was negative for each of these five
parameters across MPSP, GWP100, and FEC demonstrated that
improvements in these parameters would simultaneously
support the pursuit of economic and environmental goals.
Finally, it should be noted that the analysis here was conducted
for the baseline biorefinery design (configuration 1 with
dilution water set to zero) for the neutral fermentation
scenario. For this design, the titer of lactic acid fermentation
was a function of the pretreatment process and fermentation
yield. Thus, the titer was excluded from this analysis, but its
effects on the biorefinery were decoupled from other
parameters and discussed in detail in the following section.
Setting Targets for Fermentation. Titer, Yield, and
Productivity. As demonstrated in the sensitivity analysis, the
performance of the fermentation unit has significant
implications for MPSP, GWP100, and FEC. Thus, identifying
and pursuing specific targets for fermentation parameters have
the potential to advance the sustainability of lactic acid
production from lignocellulosic biomass. To this end, we
simulated the biorefinery across the entire titer−yield perform-
ance space (i.e., all potential combinations of values for these
two parameters) at a range of productivities to quantify how
future improvement in the fermentation unit would impact the
sustainability of the biorefinery. To enable specific titer−yield
combinations (e.g., different titers at a given yield), we
evaluated three potential process configurations in parallel
(introduced in the Methods, Figure 1A): (i) configuration 1,
dilution of the saccharified stream (after enzymatic hydrolysis)
followed by batch fermentation; (ii) configuration 2,
concentration of the saccharified stream via multi-effect
evaporation followed by batch fermentation; and (iii)
configuration 3, concentration of the saccharified stream
followed by continuous fermentation. Each of these three
configurations was optimal (i.e., lowest MPSP, GWP100, and
FEC) among feasible designs for the particular region of the
titer−yield performance space (Figure 4).
Within each configuration, MPSP benefitted from higher
titer and yield (Figure 4A), with values spanning $1.91−1.27
kg−1, $2.59−1.19 kg−1, and $3.16−1.33 kg−1 for configurations
1 through 3, respectively. Moving between configurations,
however, could lead to situations where higher titer results in
higher MPSP. For example, an MPSP of $1.57 kg−1 was
simulated for the baseline titer of 97.5 g·L−1 and yield of 0.76
g·g−1 in configuration 1 (dilution water set to zero), but
increasing the titer to 150 g·L−1 would actually increase MPSP
slightly to $1.59 kg−1. This was due to the change from
configuration 1 to 3, which was necessary to achieve the higher
titer (150 g·L−1) at the same yield. In this example, the higher
capital and operating costs associated with configuration 3
could not be offset by the economic benefits from the higher
titer, thus leading to the higher MPSP. Additionally, the
relative impact of titer and yield improvements also depended
on the location in the titer−yield performance space. In
configurations 1 and 2, improving either titer or yield could
lead to a notable reduction in the MPSP; in configuration 3,
however, the MPSP contour line was near-vertical, indicating
that increasing titer would have a limited impact on the MPSP,
while increasing yield would lead to a more substantial
reduction in the MPSP. This was due to the tradeoffs between
the capital and operating costs of the conversion and
separation processes. At a fixed productivity, a higher titer
would lead to longer fermentation time and thus a more
expensive conversion process, but the resulting more
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concentrated crude lactic acid stream would reduce the capital
and operating costs of the subsequent separation process.
Because of the separation-intensive nature of the biorefinery,
the benefits of a higher titer generally outweighed the increased
expenses, but the magnitude of the net benefits diminished
with the increasing titer. As configuration 3 was operating at
higher titers than configurations 1 and 2, the benefits from
increasing the titer were generally less substantial than the
benefits from increasing the yield.
Contrary to MPSP, GWP100 and FEC were primarily
affected by titer and were much less sensitive to yield,
decreasing from around 7.3 to 4.3 kg CO2-eq·kg−1 and from 95
to 53 MJ·kg−1 when transitioning from a titer of 75 g·L−1 to a
titer of 200 g·L−1, respectively. This observation was consistent
with the fact that these two indicators were dominated by
environmental impacts associated with natural gas and
electricity usage in the separation process. Although concen-
trating the saccharified stream required the addition of a multi-
effect evaporator unit with associated heating and cooling
demands, the costs and environmental impacts associated with
this unit were minor relative to the savings in the separation
process (<1% contribution to total capital and operating costs
and <10% contribution to GWP100 and FEC even in the most
concentration-intensive case at a titer of around 200 g·L−1 and
yield of roughly 0.5 g·g−1). Therefore, a more concentrated
lactic acid stream after fermentation would alleviate separation
needs, reduce utility usages, and lessen environmental impacts.
One counterintuitive finding was that at the same titer, FEC
increased with increasing yield. This stemmed from the fact
that at higher yields, more sugar was converted to lactic acid
rather than biogas in the anaerobic digester during wastewater
treatment, which increased the natural gas usage per kg of
lactic acid produced and thus higher FEC. For instance, if yield
increased from 0.5 to 0.8 g·g−1 at a fixed titer of 150 g·L−1, the
natural gas usage would increase from 0.68 to 0.83 kg·kg−1
lactic acid. Because natural gas accounted for >70% of FEC in
the baseline design, this resulted in higher FEC.
For MPSP, GWP100, and FEC, higher productivity would
lead to improvement (i.e., reduction) in these metric indicators
across all configurations and the entire titer−yield performance
space. However, unlike titer and yield, which affected
configurations 1 through 3 to a similar relative magnitude,
variations in productivity had much more pronounced effects
for configuration 3 than for configurations 1 and 2 (Figure 4 vs
Figures S7 and S8 in the Supporting Information). This was
due to the continuous fermentation in configuration 3, which
had a large capital cost and electricity demand for mixing. In
fact, the capital cost and electricity usage of the fermentation
unit could represent around 50% of the total capital cost and
20% of overall electricity usage in the biorefinery at the
minimum productivity examined (0.18 g·L−1·h−1), respectively.
Because the batch fermenter used for configurations 1 and 2
had a much smaller capital cost and required much less power
for mixing, the effects of productivity on the biorefinery were
more limited.
Low-pH Fermentation. In addition to the baseline
biorefinery with neutral fermentation, a low-pH fermentation
scenario was also evaluated where lime addition during
fermentation and the subsequent acidulation reactor and
gypsum filter were avoided (Figure 1B without dashed
chemicals and processes). This transition could reduce the
MPSP by $0.25−0.66 kg−1 (to $0.93−2.66 kg−1; Figure 4B),
GWP100 by 0.83−1.79 kg CO2-eq·kg−1 (to 3.08−5.55 kg CO2-
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ACS Sustainable Chem. Eng. 2021, 9, 1341−1351
ACS Sustainable Chemistry & Engineering
Figure 5. (A) MPSP and (B) GWP100 and FEC at different feedstock carbohydrate contents and prices (price only affected MPSP). In both graphs,
titer (97.5 g·L−1), yield (0.76 g·g−1), and productivity (0.89 g·L−1·h−1) of the fermentation unit were the same as the baseline. The discontinuity at
59% (baseline carbohydrate content) was due to the change in the conversion process configuration to achieve the set titer at the given yield.
Carbohydrate contents of grass clippings and switchgrass were from Roni et al.13
eq·kg−1; Figure 4D), and FEC by 5.0−15.1 MJ·kg−1 (to 42.4−
83.0 MJ·kg−1; Figure 4F). This substantial improvement was
expected as lime addition in fermentation accounted for
roughly 17% of the annual material cost, 15% of the total
GWP100, and 5% of the total FEC. Similar to the neutral
fermentation scenario, titer and yield impacted MPSP to
varying degrees across the titer−yield performance space for
low-pH fermentation (Figure 4B), but only improvements in
titer could substantially reduce GWP100 and FEC. Additionally,
benefits from higher productivity rates were largely limited to
the continuous fermentation configuration (i.e., configuration
3) and were most evident at lower productivities (Figure 4 vs
Figures S7 and S8 in the Supporting Information).
Collectively, this comprehensive evaluation of the fermenta-
tion unit across the potential performance space reveals that
although both lactic acid titer and yield are critical to the
economics of the biorefinery, titer represents the greatest
opportunity to reduce environmental impacts. Additionally,
productivity is more influential for high-titer, low-yield
combinations where the more capital- and operating-intensive
continuous fermentation is required. More specifically, across
all feasible configurations, a minimum yield of 0.45 g·g−1 must
be achieved for biorefineries employing neutral fermentation to
be competitive with the upper market price ($2.1·kg−1) at the
baseline productivity (0.89 g·L−1·h−1). Under the low-pH
fermentation scenario, however, this requirement could be
relaxed down to about 0.38 g·g−1. To have lower GWP100 and
FEC than fossil-based lactic acid (around 5.3−5.5 CO2-eq·kg−1
and 75−91 MJ·kg−1, respectively30,50), minimum titers of
about 110 g·L−1 are required for the neutral fermentation
scenario, whereas those of only around 75 g·L−1 are needed for
the low-pH fermentation scenario. Therefore, the use of acid-
resistant strains for low-pH fermentation could substantially
enhance the sustainability of the biorefinery. This research
direction appears to be particularly promising given the recent
progress in metabolic engineering, which has demonstrated
acid-resistant strains capable of reaching titers of 117−154 g·
L−1 and yields of 0.58−0.89 g·g−1 from glucose.51 Future
advancements in this area to realize similar levels of
performance for xylose and lignocellulose hydrolysates would
ultimately lead to market-competitive lactic acid with
significantly lower environmental impacts.
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pubs.acs.org/journal/ascecg Research Article
Linking Feedstocks to the Biorefinery. Because of the
diverse sources (e.g., bioenergy crops and agroindustrial
wastes) of lignocellulosic biomass, compositions and prices
of these feedstocks could vary significantly.3,13 This hetero-
geneity is particularly salient at present given that the supply
chain of lignocellulosic feedstocks has not been established and
no mature market exists for such feedstocks.3,12,52 Therefore, it
is critical to understand how changes in feedstock composition
and prices could propagate through the biorefinery to impact
the MPSP, GWP100, and FEC (Figure 5). Under the same titer
(97.5 g·L−1), yield (0.76 g·g−1), and productivity (0.89 g·L−1·
h−1) assumptions as the baseline, the cost of low-carbohydrate
feedstocks such as grass clippings (29% carbohydrate content)
needed to be lower than $50 dry ton−1 for the produced lactic
acid to be competitive with the upper market price at $2.1
kg−1, and the MPSP was not competitive with the lower
market price at $1.7 kg−1 even if the feedstock was free. If high-
carbohydrate feedstocks such as switchgrass were used, , the
biorefinery could afford a feedstock price of up to $200 dry
ton−1 and the MPSP would still be in the market range. For
GWP100 and FECtwo indicators that were almost exclusively
affected by the fermentation titerchanges in feedstock
carbohydrate content would only lead to minor changes
(6.28 to 5.88 CO2-eq·kg−1 and 79.1 to 77.3 MJ·kg−1,
respectively) across the examined 25−70% carbohydrate
range. This correlation between the feedstock carbohydrate
content, feedstock price, and quantitative economic and
environmental indicators for the biorefinery is critical for
feedstock and supply chain researchers to evaluate tradeoffs
between feedstock quality, operating decisions, and sustain-
ability targets. For example, if only around 50% carbohydrate
content can be realized at the baseline feedstock price ($71.3
dry ton−1) and the price will be doubled for feedstocks with
the baseline carbohydrate content (59%),12 it is more
economical to set 50% rather than 59% as the target for
feedstock carbohydrate content for lower MPSPs, and this
change will only have minimal impacts on GWP100 and FEC
(<1%).
Conclusions and Path toward Sustainable Lactic Acid
Biorefineries. In this study, BioSTEAMa fast, robust, and
open-source platformwas employed to automate the design,
simulation, and evaluation of a lignocellulosic biorefinery for
lactic acid production. Under the current state of technology,
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ACS Sustainable Chem. Eng. 2021, 9, 1341−1351
ACS Sustainable Chemistry & Engineering
the MPSP of the generated lactic acid was below the market
price range, but the GWP100 and FEC were higher or close to
those of fossil-derived lactic acid, primarily because of the large
heating demand of the separation process. However, improve-
ment in key technological parameters and biorefinery
operations could significantly reduce the environmental
impacts and further enhance the market competitiveness of
the biorefinery. Specifically, sustainable lactic acid production
can be achieved through a more efficient separation process
(with higher esterification and hydrolysis conversions) and
higher fermentation titers, the latter of which could be
achieved through (i) higher solid loading in pretreatment
and saccharification, (ii) concentration of the saccharified
stream, or (iii) more robust (i.e., higher yielding and acid-
resistant) microbial strains. Future developments in low-utility
separation processes such as solvent extraction and electro-
dialysis will also greatly enhance the sustainability of the
biorefinery because of the large expenses and environmental
impacts associated with product recovery. With regard to
biorefinery operations, use of renewable natural gas or
diversion of biomass to the boiler will greatly reduce
environmental impacts. As the annual lactic acid production
is around 219,000 metric tonnes for the designed biorefinery
(equivalent to around 42% of the global market volume9),
diversion of biomass can also be a risk mitigation strategy for
low market demand. Moreover, with the increasing deploy-
ment of renewable electricity and a “cleaner” grid, environ-
mental impacts of the biorefinery can be further reduced.
Overall, conclusions from this study support the production of
lactic acid from lignocellulosic feedstocks and illustrate how
agile and robust system analyses can quickly identify system
cost and environmental drivers, examine the entire feasible
technology space, balance economic and environmental
tradeoffs, and prioritize future research and development.
■
*
ASSOCIATED CONTENT
sı Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acssuschemeng.0c08055.
Supplementary descriptions of the biorefinery (including
the conversion process, separation process, and facili-
ties), selection of uncertainty distributions, literature
fermentation data, supplementary uncertainty and
sensitivity analysis results, and MPSP, GWP100, and
FEC results at different productivities (PDF)
■ AUTHOR INFORMATION
Corresponding Author
Jeremy S. Guest − Institute for Sustainability, Energy, and
Environment, University of Illinois at Urbana-Champaign,
Urbana, Illinois 61801, United States; DOE Center for
Advanced Bioenergy and Bioproducts Innovation and
Department of Civil and Environmental Engineering,
University of Illinois at Urbana-Champaign, Urbana, Illinois
61801, United States; orcid.org/0000-0003-2489-2579;
Phone: +1 (217) 244-9247; Email: jsguest@illinois.edu
Authors
Yalin Li − Institute for Sustainability, Energy, and
Environment, University of Illinois at Urbana-Champaign,
Urbana, Illinois 61801, United States; DOE Center for
Advanced Bioenergy and Bioproducts Innovation, University
1349
pubs.acs.org/journal/ascecg Research Article
of Illinois at Urbana-Champaign, Urbana, Illinois 61801,
United States; orcid.org/0000-0002-8863-4758
Sarang S. Bhagwat − DOE Center for Advanced Bioenergy
and Bioproducts Innovation and Department of Civil and
Environmental Engineering, University of Illinois at Urbana-
Champaign, Urbana, Illinois 61801, United States;
orcid.org/0000-0002-2620-2829
Yoel R. Cortés-Peña − DOE Center for Advanced Bioenergy
and Bioproducts Innovation and Department of Civil and
Environmental Engineering, University of Illinois at Urbana-
Champaign, Urbana, Illinois 61801, United States;
orcid.org/0000-0003-1742-5059
Dongwon Ki − Institute for Sustainability, Energy, and
Environment, University of Illinois at Urbana-Champaign,
Urbana, Illinois 61801, United States; DOE Center for
Advanced Bioenergy and Bioproducts Innovation, University
of Illinois at Urbana-Champaign, Urbana, Illinois 61801,
United States; orcid.org/0000-0003-2977-677X
Christopher V. Rao − DOE Center for Advanced Bioenergy
and Bioproducts Innovation and Department of Chemical
and Biomolecular Engineering, University of Illinois at
Urbana-Champaign, Urbana, Illinois 61801, United States;
orcid.org/0000-0001-5606-4204
Yong-Su Jin − DOE Center for Advanced Bioenergy and
Bioproducts Innovation and Department of Food Science and
Human Nutrition, University of Illinois at Urbana-
Champaign, Urbana, Illinois 61801, United States;
orcid.org/0000-0002-4464-9536
Complete contact information is available at:
https://pubs.acs.org/10.1021/acssuschemeng.0c08055
Notes
The authors declare no competing financial interest.
■
ACKNOWLEDGMENTS
We would like to thank Dr. Eberhard Morgenroth for
providing advice on the biorefinery design. This work was
funded by the DOE Center for Advanced Bioenergy and
Bioproducts Innovation (U.S. Department of Energy, Office of
Science, Office of Biological and Environmental Research
under Award Number DE-SC0018420). Any opinions,
findings, and conclusions or recommendations expressed in
this publication are those of the author(s) and do not
necessarily reflect the views of the U.S. Department of Energy.
■
REFERENCES
(1) IPCC. Global Warming of 1.5°C; Intergovernmental Panel on
Climate Change, 2018.
(2) Bailey, A.; Leong, G. J.; Fitzgerald, N. Bioproducts to Enable
Biofuels Workshop Summary Report; DOE/EE-1294; Office of Energy
Efficiency and Renewable Energy (EERE): Washington, DC (United
States), 2015.
(3) U.S. Department of Energy. 2016 Billion-Ton Report: Economic
Availability of Feedstocks; DOE/EE-1440, 2016; Vol. 1.
(4) de Oliveira, R. A.; Komesu, A.; Vaz Rossell, C. E.; Maciel Filho,
R. Challenges and Opportunities in Lactic Acid Bioprocess Design
From Economic to Production Aspects. Biochem. Eng. J. 2018, 133,
219−239.
(5) Naqvi, M.; Yan, J. First-Generation Biofuels. Handbook of Clean
Energy Systems; American Cancer Society, 2015; pp 1−18.
(6) Jeswani, H. K.; Chilvers, A.; Azapagic, A. Environmental
Sustainability of Biofuels: A Review. Proc. R. Soc. A 2020, 476,
20200351.
https://dx.doi.org/10.1021/acssuschemeng.0c08055
ACS Sustainable Chem. Eng. 2021, 9, 1341−1351
ACS Sustainable Chemistry & Engineering
(7) Bozell, J. J.; Petersen, G. R. Technology Development for the
Production of Biobased Products from Biorefinery Carbohydrates
the US Department of Energy’s “Top 10” Revisited. Green Chem.
2010, 12, 539−554.
(8) Biddy, M. J.; Scarlata, C.; Kinchin, C. Chemicals from Biomass: A
Market Assessment of Bioproducts with Near-Term Potential; NREL/
TP-5100-65509; National Renewable Energy Lab. (NREL): Golden,
CO (United States), 2016..
(9) IHS Markit. Chemical Economics Handbook − Lactic Acid, Its
Salts and Esters, 2018.
(10) Wang, Y.; Tashiro, Y.; Sonomoto, K. Fermentative Production
of Lactic Acid from Renewable Materials: Recent Achievements,
Prospects, and Limits. J. Biosci. Bioeng. 2015, 119, 10−18.
(11) Pereira, C. S. M.; Silva, V. M. T. M.; Rodrigues, A. E. Ethyl
Lactate as a Solvent: Properties, Applications and Production
Processes − a Review. Green Chem. 2011, 13, 2658−2671.
(12) Hartley, D. S.; Thompson, D. N.; Griffel, L. M.; Nguyen, Q. A.;
Roni, M. S. Effect of Biomass Properties and System Configuration on
the Operating Effectiveness of Biomass to Biofuel Systems. ACS
Sustainable Chem. Eng. 2020, 8, 7267−7277.
(13) Roni, M. S.; Hartley, D. S.; Griffel, M.; Hu, H.; Nguyen, Q. A.;
Cai, H.; Thompson, D. N. Herbaceous Feedstock 2018 State of
Technology Report; INL/EXT-18-51654-Rev000; Idaho National Lab.
(INL): Idaho Falls, ID (United States), 2020.
(14) BioSTEAM Development Group. BioSTEAM: The Biorefinery
Simulation and Techno-Economic Analysis Modules. https://github.
com/BioSTEAMDevelopmentGroup/biosteam (accessed Apr 17,
2020).
(15) Cortes-Peña, Y.; Kumar, D.; Singh, V.; Guest, J. S. BioSTEAM:
A Fast and Flexible Platform for the Design, Simulation, and Techno-
Economic Analysis of Biorefineries under Uncertainty. ACS
Sustainable Chem. Eng. 2020, 8, 3302−3310.
(16) Cortés-Peña, Y. Thermosteam: BioSTEAM’s Premier Thermo-
dynamic Engine. J. Open Source Software 2020, 5, 2814.
(17) Shi, R.; Guest, J. S. BioSTEAM-LCA: An Integrated Modeling
Framework for Agile Life Cycle Assessment of Biorefineries under
Uncertainty. ACS Sustainable Chem. Eng. 2020, 8, 18903.
(18) Humbird, D.; Davis, R.; Tao, L.; Kinchin, C.; Hsu, D.; Aden,
A.; Schoen, P.; Lukas, J.; Olthof, B.; Worley, M.; Sexton, D.;
Dudgeon, D. Process Design and Economics for Biochemical Conversion
of Lignocellulosic Biomass to Ethanol: Dilute-Acid Pretreatment and
Enzymatic Hydrolysis of Corn Stover; Technical Report NREL/TP-
5100-47764; National Renewable Energy Lab (NREL), 2011.
(19) Jacobson, J. J.; Roni, M. S.; Cafferty, K. G.; Kenney, K.; Searcy,
E.; Hansen, J. Biomass Feedstock and Conversion Supply System Design
and Analysis; INL/EXT-14-32377; Idaho National Lab. (INL), 2014.
(20) Baral, N. R.; Kavvada, O.; Mendez-Perez, D.; Mukhopadhyay,
A.; Lee, T. S.; Simmons, B. A.; Scown, C. D. Techno-Economic
Analysis and Life-Cycle Greenhouse Gas Mitigation Cost of Five
Routes to Bio-Jet Fuel Blendstocks. Energy Environ. Sci. 2019, 12,
807−824.
(21) Chen, X.; Kuhn, E.; Jennings, E. W.; Nelson, R.; Tao, L.;
Zhang, M.; Tucker, M. P. DMR (Deacetylation and Mechanical
Refining) Processing of Corn Stover Achieves High Monomeric Sugar
Concentrations (230 g L−1) during Enzymatic Hydrolysis and High
Ethanol Concentrations (>10% v/v) during Fermentation without
Hydrolysate Purification or Concentration. Energy Environ. Sci. 2016,
9, 1237−1245.
(22) Davis, R. E.; Grundl, N. J.; Tao, L.; Biddy, M. J.; Tan, E. C.;
Beckham, G. T.; Humbird, D.; Thompson, D. N.; Roni, M. S. Process
Design and Economics for the Conversion of Lignocellulosic Biomass to
Hydrocarbon Fuels and Coproducts: 2018 Biochemical Design Case
Update; NREL/TP-5100-71949; NREL, 2018.
(23) Cheng, M. H.; Huang, H.; Dien, B. S.; Singh, V. The Costs of
Sugar Production from Different Feedstocks and Processing
Technologies. Biofuels, Bioprod. Biorefin. 2019, 13, 723−739.
(24) Maas, R. H. W.; Bakker, R. R.; Eggink, G.; Weusthuis, R. A.
Lactic Acid Production from Xylose by the Fungus Rhizopus Oryzae.
Appl. Microbiol. Biotechnol. 2006, 72, 861−868.
1350
pubs.acs.org/journal/ascecg Research Article
(25) Zhao, W.; Sun, X.; Wang, Q.; Ma, H.; Teng, Y. Lactic Acid
Recovery from Fermentation Broth of Kitchen Garbage by
Esterification and Hydrolysis Method. Biomass Bioenergy 2009, 33,
21−25.
(26) Gezae Daful, A.; Görgens, J. F. Techno-Economic Analysis and
Environmental Impact Assessment of Lignocellulosic Lactic Acid
Production. Chem. Eng. Sci. 2017, 162, 53−65.
(27) BioSTEAM Development Group. Bioindustrial-Park: Bio-
STEAM’s Premier Repository for Biorefinery Models and Results.
https://github.com/BioSTEAMDevelopmentGroup/Bioindustrial-
Park (accessed Apr 17, 2020).
(28) Dunn, J. B.; Mueller, S.; Kwon, H.-y.; Wang, M. Q. Land-Use
Change and Greenhouse Gas Emissions from Corn and Cellulosic
Ethanol. Biotechnol. Biofuels 2013, 6, 51.
(29) Pavlenko, N.; Searle, S. A Comparison of Induced Land-Use
Change Emissions Estimates from Energy Crops; International Concil on
Clean Transportation, 2018; p 44.
(30) Dunn, J. B.; Adom, F.; Sather, N.; Han, J.; Snyder, S.; He, C.;
Gong, J.; Yue, D.; You, F. Life-Cycle Analysis of Bioproducts and Their
Conventional Counterparts in GREET; ANL/ESD-14/9 Rev.; Argonne
National Lab. (ANL): Argonne, IL (United States), 2015.
(31) Manandhar, A.; Shah, A. Techno-Economic Analysis of Bio-
Based Lactic Acid Production Utilizing Corn Grain as Feedstock.
Processes 2020, 8, 199.
(32) U.S. EPA. Lifecycle Analysis of Greenhouse Gas Emissions
under the Renewable Fuel Standard. https://www.epa.gov/
renewable-fuel-standard-program/lifecycle-analysis-greenhouse-gas-
emissions-under-renewable-fuel (accessed Aug 10, 2020).
(33) Adom, F. K.; Dunn, J. B. Life Cycle Analysis of Corn-Stover-
Derived Polymer-Grade l-Lactic Acid and Ethyl Lactate: Greenhouse
Gas Emissions and Fossil Energy Consumption. Biofuels, Bioprod.
Biorefin. 2017, 11, 258−268.
(34) Liu, G.; Sun, J.; Zhang, J.; Tu, Y.; Bao, J. High Titer L-Lactic
Acid Production from Corn Stover with Minimum Wastewater
Generation and Techno-Economic Evaluation Based on Aspen plus
Modeling. Bioresour. Technol. 2015, 198, 803−810.
(35) Han, X.; Hong, F.; Liu, G.; Bao, J. An Approach of Utilizing
Water-Soluble Carbohydrates in Lignocellulose Feedstock for
Promotion of Cellulosic l-Lactic Acid Production. J. Agric. Food
Chem. 2018, 66, 10225−10232.
(36) Wei, C.; Liu, G.; Zhang, J.; Bao, J. Elevating Fermentation Yield
of Cellulosic Lactic Acid in Calcium Lactate Form from Corn Stover
Feedstock. Ind. Crops Prod. 2018, 126, 415−420.
(37) Gezae Daful, A.; Görgens, J. F. Techno-Economic Analysis and
Environmental Impact Assessment of Lignocellulosic Lactic Acid
Production. Chem. Eng. Sci. 2017, 162, 53−65.
(38) Mandegari, M. A.; Farzad, S.; van Rensburg, E.; Görgens, J. F.
Multi-criteria Analysis of a Biorefinery for Co-production of Lactic
Acid and Ethanol from Sugarcane Lignocellulose. Biofuels, Bioprod.
Biorefin. 2017, 11, 971−990.
(39) Mandegari, M.; Farzad, S.; Görgens, J. F. A New Insight into
Sugarcane Biorefineries with Fossil Fuel Co-Combustion: Techno-
Economic Analysis and Life Cycle Assessment. Energy Convers.
Manage. 2018, 165, 76−91.
(40) Tao, L.; Schell, D.; Davis, R.; Tan, E.; Elander, R.; Bratis, A.
NREL 2012 Achievement of Ethanol Cost Targets: Biochemical Ethanol
Fermentation via Dilute-Acid Pretreatment and Enzymatic Hydrolysis of
Corn Stover; NREL/TP-5100-61563; National Renewable Energy
Lab. (NREL): Golden, CO (United States), 2014.
(41) Pachón, E. R.; Vaskan, P.; Raman, J. K.; Gnansounou, E.
Transition of a South African Sugar Mill towards a Biorefinery. A
Feasibility Assessment. Appl. Energy 2018, 229, 1−17.
(42) Pachón, E. R.; Mandade, P.; Gnansounou, E. Conversion of
Vine Shoots into Bioethanol and Chemicals: Prospective LCA of
Biorefinery Concept. Bioresour. Technol. 2020, 303, 122946.
(43) Argonne National Laboratory. The Greenhouse gases,
Regulated Emissions, and Energy use in Transportation (GREET)
Model. https://greet.es.anl.gov/ (accessed Aug 25, 2020).
https://dx.doi.org/10.1021/acssuschemeng.0c08055
ACS Sustainable Chem. Eng. 2021, 9, 1341−1351
ACS Sustainable Chemistry & Engineering pubs.acs.org/journal/ascecg Research Article

(44) Zhang, Y.; Ma, L.; Yang, J. Kinetics of Esterification of Lactic

Acid with Ethanol Catalyzed by Cation-Exchange Resins. React. Funct.
Polym. 2004, 61, 101−114.
(45) Pereira, C. S. M.; Pinho, S. P.; Silva, V. M. T. M.; Rodrigues, A.
E. Thermodynamic Equilibrium and Reaction Kinetics for the
Esterification of Lactic Acid with Ethanol Catalyzed by Acid Ion-
Exchange Resin. Ind. Eng. Chem. Res. 2008, 47, 1453−1463.
(46) Delgado, P.; Sanz, M. T.; Beltrán, S. Kinetic Study for
Esterification of Lactic Acid with Ethanol and Hydrolysis of Ethyl
Lactate Using an Ion-Exchange Resin Catalyst. Chem. Eng. J. 2007,
126, 111−118.
(47) Barve, P. P.; Kulkarni, B. D.; Nene, S. N.; Shinde, R. W.; Gupte,
M. Y.; Joshi, C. N.; Thite, G. A.; Chavan, V. B.; Deshpande, T. R.
Process for Preparing L- (+) -Lactic Acid. U.S. Patent 7,820,859 B2,
October 26, 2010.
(48) Dahmen, N.; Lewandowski, I.; Zibek, S.; Weidtmann, A.
Integrated Lignocellulosic Value Chains in a Growing Bioeconomy:
Status Quo and Perspectives. GCB Bioenergy 2019, 11, 107−117.
(49) Farzad, S.; Mandegari, M. A.; Guo, M.; Haigh, K. F.; Shah, N.;
Görgens, J. F. Multi-Product Biorefineries from Lignocelluloses: A
Pathway to Revitalisation of the Sugar Industry? Biotechnol. Biofuels
2017, 10, 87.
(50) ecoinvent 3.6. https://www.ecoinvent.org/home.html (ac-
cessed Aug 26, 2020).
(51) Park, H. J.; Bae, J. H.; Ko, H. J.; Lee, S. H.; Sung, B. H.; Han, J.
I.; Sohn, J. H. Low-PH Production of d-Lactic Acid Using Newly
Isolated Acid Tolerant Yeast Pichia Kudriavzevii NG7. Biotechnol.
Bioeng. 2018, 115, 2232−2242.
(52) Sievers, D. A.; Kuhn, E. M.; Thompson, V. S.; Yancey, N. A.;
Hoover, A. N.; Resch, M. G.; Wolfrum, E. J. Throughput, Reliability,
and Yields of a Pilot-Scale Conversion Process for Production of
Fermentable Sugars from Lignocellulosic Biomass: A Study on
Feedstock Ash and Moisture. ACS Sustainable Chem. Eng. 2020, 8,
2008−2015.

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