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Monosodium Glutamate (MSG) Production via Fermentation - Process Modeling

and Techno-Economic Assessment (TEA) using SuperPro Designer

Preprint · September 2020

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 Production of Monosodium
Glutamate (MSG)
Modeling and Evaluation with

SuperPro Designer®
by

Amir Mustafa, Nikiforos Misailidis and Demetri Petrides

This is the ReadMe file of a SuperPro Designer example that deals with process modeling, cost analysis
and optimization of Monosodium Glutamate (MSG) production via fermentation. The flowsheet of the
process is appended to the bottom of this document. You may test-drive the model by downloading the
functional evaluation edition of SuperPro Designer from the downloads page of our website
(www.intelligen.com). The files of this example can be found in the Examples \ Food Processing \ MSG
folder. The default installation path of the SuperPro Designer Examples folder follows below.

C:\ Users \ Public \ Public Documents \ Intelligen \ SuperPro Designer \ v11 \ Process Library \ Examples

If you have any questions about this example and SuperPro Designer in general, please send an email
message to dpetrides@intelligen.com

INTELLIGEN, INC.
Simulation, Design, and Scheduling Tools
For the Process Manufacturing Industries
www.intelligen.com

Intelligen, Inc. Page 1

Introduction

Monosodium Glutamate (MSG) is the sodium salt of glutamic acid, which was first prepared in 1908 by a
Japanese biochemist (Kikunae Ikeda) from an edible seaweed. Glutamic acid is naturally found in many
food items such as tomato, cheese and meat and gives these foods a savory flavor known as umami [2].
Monosodium glutamate is used as a flavor enhancing ingredient in many Japanese and Chinese foods and
forms a basis of a roughly $7.2 billion Industry (2020) [5].

(S)-glutamic acid (S)-monosodium glutamate (MSG)

(MSG)
Figure 1. Schematic structure of (s)- glutamic acid and (s)-mono sodium glutamate (MSG)

Glutamic acid is the largest produced amino acid in the world. There are four main ways to obtain glutamic
acid for commercial use.

• Extraction from natural sources by hydrolysis with hydrochloric acid (1909-1962)

• Chemical synthesis starting with acrylonitrile (1962-1973)
• Bacterial Fermentation (the method analyzed in this example)
• Enzymatic catalysis [1]

This example analyzes the production of MSG via bacterial fermentation.

MSG is mostly found as monohydrate crystals, a white and odorless powder. The solid contains cations of
Na+ and glutamate anions in zwitterionic form. In aqueous solutions, it dissociates into glutamate and
sodium ions [2].

MSG is readily soluble in water and is generally stable under food processing conditions. MSG does not
break down during cooking.

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 Figure 2. Schematic structure of Monosodium Glutamate [2].

Table 1. Chemical Properties of Monosodium Glutamate [2] [3].

IUPAC name: sodium (2S)-2-amino-5-hydroxy-5-oxo-pentanoate

Chemical Formula C5H8NNaO4

Molar Mass 169.1 g/mol (anhydrous), 187.125 g/mol (hydrous)

Density 1.63 g/cm3

Melting Point 232 oC

Solubility in H2O 740 g/L

The first biotechnological production of Glutamic Acid was discovered in 1950 with E. Coli in very small
quantities. But very soon it was discovered that large quantities of Glutamic Acid can be produced by
another bacterium, which was later named Corynebacterium glutamicum (C. glutamicum), from
carbohydrates according to the following stoichiometry:

C12H22O11 + 3O2 + 2NH3 → 2C5H9O4N + 2CO2 + 5H2O

The continuous optimization of the large scale biotechnological Glutamic Acid production with C.
glutamicum resulted ultimately in more economical production process compared to the chemical
processes [1]. The global annual production of MSG exceeds 3 million metric tons [4][6]. The monetary
value per kilogram of MSG varies between US$1.30 and US$1.8 depending on the manufacturer and
quality of the product.

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Process Description

The development of this example was based on data available in the technical literature in the public
domain and assumptions based on our engineering judgment. The flowsheet of the process is appended
to the bottom of this document.

For the fermentation, a strain of Corynebacterium glutamicum (C. glutamicum) is used to transform
glucose and ammonia into glutamic acid. The conceptual plant produces about 50 metric tons (MT) of
monosodium glutamate monohydrate crystals per batch. The plant operates for about 7920 hours per
year, processing 977 batches per year. This translates to a total annual production of approximately
48,917 MT/yr.

For reporting and analysis purposes, the process has been divided into three sections:

➢ Fermentation

➢ Purification

➢ Water Supply

A flowsheet section is a set of associated unit procedures (processing steps). The unit procedure icons of
each section are displayed in a unique color. In this model, black color is used for fermentation, cyan for
water supply and orange for purification. For more information on how to specify flowsheet sections and
edit their properties, please refer to chapter 7.1 of the SuperPro Manual or consult the online help facility
(search for “sections”).

Fermentation Section

The fermentation section consists of a train of two seed fermentors and the main production fermentors.
All fermentors use the same medium. The fermentation medium is prepared using two major components;
glucose, which is the main carbon source, and ‘’Nutrients”’, which is a mixture of substances that promote
microbial growth such as biotin. The Nitrogen source of the fermentation is added prior and during
fermentation in the form of Ammonium Hydroxide (NH4OH).

Glucose syrup (70% dry solids) and Nutrients are mixed with water in a blending tank (V-101) to obtain
appropriate medium for fermentation. After charging all the necessary ingredients in the blending tank the
mixture is thoroughly agitated for around 30 mins and then passed through a sterilizer (ST-101) to ensure
the prepared media is free of any foreign microorganism contamination. The sterilized media is then

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divided into three different streams using a bulk flow 3-way splitter (FSP-101). The inoculum preparation
seed fermenter (SFR-101), uses 0.4% of the total media preparation.

The broth of SFR-101 is then sent to the next seed fermentor (SFR-102), which is about ten times the
size of SFR-101 and produces the inoculum for the production fermentors (FR-101). All fermentation
procedures include the following operations:

- SIP (Steam-In-Place). At the beginning of each batch a SIP operation ensures sterile conditions
prior to pulling in the substrate, water and inoculum.
- Pull-In-Media. The substrate syrup is added to the fermentation vessels. The substrate syrup is
distributed to the fermentation vessels via a flow splitter (FSP-101).
- Pull-In-Water. The substrate syrup is diluted with water in the fermentor. The amount of water
needed is defined by the initial target concentration of glucose which for this fermentation was set
at 10% w/w. The Pull in Water operation is scheduled to start right after the end of the Pull In
Media operation.
- Transfer-In NH4OH. pH is adjusted with the addition of Ammonium Hydroxide, which is also the
main Nitrogen source for the microorganism.
- Pull-In Inoculum. The Inoculum is pulled in from the previous seed fermentor.
- Ferment. The microorganisms grow and convert glucose and other nutrients into glutamic acid.
In the main production fermentors, additional substrate is supplied in fed-batch model during
fermentation. Oxygen is supplied at a rate of 1 VVM to the seed fermentors and 0.5 VVM to the
production fermentors.
- Transfer-Out. At the end of the fermentation, the broth is transferred to the next fermentor or
ultimately to the downstream buffer tank (V-104).
- CIP (Clean-In-Place). A CIP operation takes place at the end of each batch, which includes an
initial water flush, wash with 2% NaOH and a final water wash.

Material transformation in all fermentation operations was represented by the following two reactions. The
95% conversion of the second reaction is based on glucose not consumed by the first reaction.

Fermentation Reactions - Molar Stoichiometry Conversion

Glucose + 0.94NH4OH + Nutrients + 2.8O2 → 4Biomass +3CO2 + 5H2O 23%

2Glucose + 2NH4OH + 3O2→ 2Glutamic-Acid + 2CO2 + 8H2O 95%

The duration of the fermentation operation in the two inoculum procedures is 14 hours. Air is supplied at a
rate of 1 VVM and the temperature is maintained at 32 0C. The duration of the fermentation operation in

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the production fermentors is 48 hours. Air is supplied at a rate of 0.5 VVM and the temperature is
maintained at 32 0C. Media are supplied to the production fermentors in fed-batch mode to prevent cell
growth inhibition.

Air is supplied to the seed and production fermentors by a compressor (G-101). Ambient air is first
sterilized by an air filter (AF-101) and then the compressor increases its pressure by 2 bar. The
compressed air is distributed to the seed and production fermentors using a 3-way flow-distribution
procedure (FDIS-102) which collects the demand of all fermentation operations and adjusts the flowrate
of the “Air” inlet stream which is in “Auto-Adjust” mode. For the sake of simplicity, it was assumed that the
procedures of the aeration line operate in continuous mode. This was specified by right-clicking on the
procedure icons, selecting Procedure Data and setting the Operating Mode to Continuous.

Ammonium hydroxide is used for pH adjustment as well as a source of Nitrogen for microorganism
growth. An aqueous ammonium hydroxide solution (26% w/w) is prepared in a blending tank (V-102),
sterile filtered in DE-101 and distributed to all the fermenters via 3-way flow splitter (FDIS -103).

The duration of the production fermentation procedure is 55 hours. There are 7 (seven) identical
production fermentors operating in staggered mode. A new production fermentation batch is initiated
every 8 hours. Similarly, there are multiple seed fermentors operating in staggered mode.

After the end of the main fermentation the broth is transferred to a storage tank V-104. This tank acts as a
buffer tank that receives material from the fermentors that operate on batch mode, and feeds
continuously the downstream section, which operates in continuous mode. The broth is then sent to a
continuous rotary vacuum filter (RVF-101) where almost all of the biomass is removed.

Purification Section

The product is in solution. Cell mass is removed using a rotary vacuum filter (RFV-101). The cake is
washed with water to minimize product losses. The filtrate of the rotary vacuum filter, which contains the
glutamic acid, is heated to 52 0C and then passed through a mixed bed Ion Exchanger (INX-101), which
removes the ions contained in the broth. The Ion Exchanger includes the following operations:

- LOAD. During loading ions present in the inlet stream are bound to the resin. The loading
duration was set at 2 hours
- WASH. The column is washed with 2 Bed Volumes (BV) of water over a period of 30 min.
- REGENERATE-1. The column is regenerated with 2 BV of 1 M HCl solution over a period of 30
minutes.
- REGENERATE-2. The column is regenerated with 2 BV of 1M NaOH solution over a period of 30
minutes.

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There are two Ion Exchange units operating in staggered mode that alternate in operation every 2 hours.
While one column is in load mode, the other column undergoes washing and regeneration.

After the ion exchanger, the glutamic acid is neutralized with sodium hydroxide (NaOH) in a continuous
neutralizer (NT-101) to produce Monosodium Glutamate (MSG) according to the following reaction.

Glutamic Acid Neutralization - Molar Stoichiometry Conversion

Glutamic-Acid + NaOH → MSG + H2O 100%

Following neutralization the product solution is heated to 60 0C using a heat exchanger (HX-103) and
sent for discoloration (organic impurity removal) to Granular Activated Carbon unit (GAC-101)., GAC 101
receives backwash water from the water supply section through FDIS-104. The GAC procedure includes
the following operations.

- LOAD. During loading almost all organic matter such as cell mass, unreacted glucose and
nutrients are bound to the activated carbon of the column. The duration of this operation is 60
mins.
- WASH. The column is washed with 3 BV of water over a period of 30 mins to remove all bound
impurities.

Like the Ion Exchanger, there are two GAC columns operating in staggered mode that alternate in
operation every 60. While one column is in load mode, the other column undergoes washing.

The output of the GAC column is sent to the evaporator feed tank V-103, where it is mixed with recycled
streams, which will be later analyzed. A four-stage continuous evaporator (EV-101) concentrates the
solution at a final water content of around 21% (around 92% of the water is evaporated). The condensate
and the vapor streams are sent to the water supply section for recycling. The concentrated product
solution is sent to a continuous crystallizer (R-101) where it is cooled down to 15 0C using chilled water
and the solubilized MSG is converted to its crystal form, MSG-Cr, according to the following molar
stoichiometry and conversion.

MSG Crystallization - Molar Stoichiometry Conversion

MSG + H2O → MSG-Cr 56%

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The crystals are recovered and washed using a set of three basket centrifuges (BCF-101). The basket
centrifugation procedure includes the following operations.

- FILTER. The MSG crystals are separated from the mother liquor. The duration of this operation is
60 min, the average filtrate flux is 200 L/m2-h and the LOD is 8%.
- CAKE WASH. The cake is washed with 0.4 volumes of water per volume of cake over a period of
15 min.
- TRANSFER-OUT. The washed cake is transferred out to a rotary drier (RDR-101) for drying.

The three centrifuges process of the material of a batch in 5 (five) cycles. This is specified by right-clicking
on the procedure icon, selecting Procedure Data and changing the value of the Number of Cycles per
Batch at the top of the window. The multiple cycles per batch reduce the number of required centrifuges.

Around 25% of the mother liquor of the centrifuge (stream S-130) is separated by a flow splitter (FSP-
103) and sent to the CIP Waste receiving storage unit. This is specified by right clicking on stream S-151,
selecting Assign Receiving Storage Unit and the choosing the CIP Waste (Aqueous Waste) option from
the drop-down menu. The remainder mother liquor (75% of total) is recycled back to the evaporator feed
tank (V-103). Similarly, 100% of the high-purity wash water (stream S-150) is recycled back to the
evaporator feed tank (V-103).

The washed MSG crystals are sent to a rotary drier (RDR-101) which removes 99% of the water using air
heated with steam. The final product has a final purity of more than 99%.

Water Supply Section

A large amount of water is used in the fermentation section. This water is ultimately separated from the
product stream in the evaporator (EV-101). The vapor of the last stage of EV-101 is condensed using a
condenser (HX-104) and it is mixed with the remaining vapor condensate originating from the first three
stages of the evaporator (stream S-165). A Flow Adjusting procedure (FAD-101) along with a Flow
Distribution procedure (FDIS-104) manage the reuse of a good fraction of the condensate. More
specifically, the water needs of the Purification Section are fully met by recycled condensate. It is also
possible to recycle the unused condensate back to the fermentation section and reduce further the net
water needs of the overall process.

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Process Scheduling and Debottlenecking

The overall batch time for this process is approximately 102 hours. This is the time elapsed from the
beginning of a given batch (i.e., the preparation of fermentation media) to the end of that batch
(generation of the pure product). However, the availability of multiple fermentors operating in staggered
mode enables the overall process to operate with a recipe cycle time is of only 8 hours. Consequently, a
new batch is initiated every 8 hours leading to processing of 978 batches per year.

The schedule of the process can be visualized with the Equipment Occupancy Chart (EOC) which can be
generated by selecting Charts >> Equipment Occupancy >> Multiple Batches. A portion of the EOC,
showing 10 consecutive batches of this process is displayed in Figure 3.

Figure 3. Equipment Occupancy chart for 10 batches.

Note the multiple production fermentors (FR-101, FR-101a, FR-101b, FR-101c, FR-101d, FR-101e, FR-
101f) operating in staggered mode (alternating from batch to batch) and reducing the overall recipe cycle
time to 8 hours. In batch processing, when a procedure has a long duration, it is common to assign
multiple equipment unit to that procedure operating in staggered mode to reduce the overall recipe cycle
time and increase the throughput of the process.

Another chart of interest to visualize the schedule of a batch process is the Operations Gantt chart (in the
MS Project style). The chart displays detailed scheduling information for one or multiple batches. The Gantt

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chart for a single batch is displayed by selecting Charts >> Gantt Charts >> Operations GC. A portion of
the Gantt chart is displayed in Figure 4. The dark blue and cyan bars represent the durations of procedures
and their operations, respectively.

Figure 4. Portion of the Gantt chart of a single batch of MSG production.

The Gantt chart enables users to visualize the execution of a batch process in detail. In addition, the Gantt
chart facilitates editing of batch processes. Double-clicking on any of its bars bring up the dialog of the
corresponding entity (e.g., operation, procedure, recipe etc.). The simulation calculations can then be
redone and the chart can be updated by clicking on the refresh button on the chart.

SuperPro Designer can export the scheduling data to MS Project by selecting File >> Export to MS
Project XML File. Also, recipe data can be exported to SchedulePro by selecting File >> Export to
SchedulePro’s Recipe DB. SchedulePro is a resource management, production planning and scheduling
tool available from Intelligen. Please consult the SuperPro Designer manual or its Help facility for additional
information on these two exporting options.

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Material Requirements

Table 2 displays the raw material requirements in kg/year, kg/batch, and kg/kg MP (“MP” = main product;
MSG-Cr in this case) for this process. This table was extracted from the RTF version of the Materials &
Streams report, which can be generated by selecting Reports >> Materials & Streams from the main
menu bar of the SuperPro Designer. The format of the report can be specified through the dialog that is
displayed when you select Reports >> Options from the main menu bar of SuperPro Designer. It is worth
reminding that these amounts refer to an annual production rate of approximately 48,900 metric tons as
stated in the Process Description above.

Table 2. Material Requirement for the Entire Process.

Material MT/yr MT/batch MT/kg MP

Air 329,599 337.01 0.01
Glucose Solution 108,558 111.00 0.00
HCl (1 M) 26,749 27.35 0.00
NaOH (1 M) 27,623 28.24 0.00
NaOH (2%) 9,942 10.17 0.00
NH4OH 14,181 14.50 0.00
Nutrients 2,249 2.30 0.00
Sodium Hydroxide 12,374 12.65 0.00
Water 187,611 191.83 0.00
TOTAL 718,888 735.06 0.01

Cost Analysis

SuperPro Designer performs thorough cost analysis, estimating capital (CAPEX) as well as operating
(OPEX) costs, and generates the following three pertinent reports (through the Reports menu): Economic
Evaluation Report (EER), Cash Flow Analysis Report (CFR), Itemized Cost Report (ICR). Table 3
displays the Executive Summary of the Economic Evaluation Report. Reports can be generated in
various formats (e.g., PDF, RTF, XLS, etc.,) specified through Reports >> Options.

For a fermentation plant that produces approximately 48,900 MT of MSG monohydrate crystals per year,
the total capital investment was estimated to be around $76.2 million, while the annual operating cost was
calculated to be $65.4 million. The resulting unit production cost is $1.33/kg of product. Assuming a
selling price of $1.5/kg of MSG monohydrate crystals, the gross margin would be 11%, the return on

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investment 16.6%, and the payback time around 6 years. These metrics suggest that this process for
MSG production is economically feasible.

Table 2. Executive Summary

EXECUTIVE SUMMARY (2020 prices)

Total Capital Investment 76,235,000 $

Capital Investment Charged to This Project 76,235,000 $
Operating Cost 65,405,000 $/yr
Savings (due to Heat Recovery) 66,970 $/yr
Revenues 73,375,000 $/yr
Batch Size 50,009.42 kg MP
Cost Basis Annual Rate 48,916,443 kg MP/yr
Unit Production Cost 1.34 $/kg MP
Net Unit Production Cost 1.34 $/kg MP
Unit Production Revenue 1.50 $/kg MP
Gross Margin 10.95 %
Return On Investment 16.58 %
Payback Time 6.03 years
IRR (After Taxes) 12.67 %
NPV (at 3.0% Interest) 102,233,000 $
MP = Total Flow of Stream 'MSG'

Figure 5 displays the annual operating cost breakdown, which is also a part of EER. This type of chart
can be included in the report by selecting Reports >> Options and activating the Include Charts option
on the lower right corner of the dialog. The chart shows that the raw materials cost is the most important
accounting for 62% of the overall operating cost, followed by facility dependent (21%) and utilities (8%).

Figure 5. Annual Operating Cost Breakdown.

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Summary
Our objective with this example was to present a simple monosodium glutamate production model in
SuperPro Designer that is easy to understand and follow. As indicated in the preceding analysis, a plant
with capacity of around 48,900 metric tons of monosodium glutamate per year requires a total CAPEX of
around $76 million and annual operating expenditures (including depreciation) of around $65.4 million.
The predominant cost is the cost of raw materials, especially the glucose syrup, followed by the facility-
dependent costs. The payback time for such as investment was estimated to be around 6 years.

Intelligen, Inc. Page 13

References

1. The Monosodium Glutamate Story: The Commercial Production of MSG and Other Amino Acids
by Addison Ault, Department of Chemistry, Cornell College, Mount Vernon, IA 52314;
aault@cornellcollege.edu. (Chemistry for Everyone)
2. Wikipedia, https://en.wikipedia.org/wiki/Monosodium_glutamate
3. https://foodadditives.net/flavor-enhancer/msg/
4. https://spendmatters.com/2014/02/03/msg-worlds-well-known-secret-ingredient/
5. https://www.marketsandmarkets.com/Market-Reports/savory-ingredients-market-193325783.html
6. https://www.gminsights.com/industry-analysis/glutamic-acid-and-monosodium-glutamate-msg-
market

Intelligen, Inc. Page 14

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