Review
New opportunities for biocatalysis:
making pharmaceutical processes
greener
John M. Woodley
Center for BioProcess Engineering, Department of Chemical and Biochemical Engineering, Technical University of Denmark,
DK-2800 Lyngby, Denmark
The pharmaceutical industry requires synthetic routes to
be environmentally compatible as well as to fulfill the
demands of process economics and product specifica-
tion and to continually reduce development times. Bio-
catalysis has the potential to deliver ‘greener’ chemical
syntheses, and in this review some of these opportu-
nities are outlined and outstanding challenges pre-
sented. Future development will require research
targeted towards increased commercial availability of
key enzymes, as well as the improvement of enzyme
stability and substrate repertoire, to fully realize the
potential of biocatalysis for making pharmaceutical pro-
cesses greener.
Introduction
Biotechnology offers many possibilities for new medical
therapies and the manufacture of new pharmaceuticals,
including the manufacture of small-molecule pharmaceu-
ticals via biocatalysis. In a recent article [1], new oppor-
tunities for biocatalysis in the pharmaceutical industry
were highlighted. These opportunities have arisen from
new scientific developments (such as protein engineering),
engineering developments (such as accelerated process
development) and the increased availability of interesting
enzymes (such as nitrilases and oxynitrilases). However,
new opportunities have also arisen from new industrial
requirements. It is well established that pharmaceutical
companies have to develop processes that reach a particu-
lar specification under given economic constraints.
Because of the limited patent life of new pharmaceuticals,
companies need to develop processes rapidly to offset the
high investment costs in pharmaceutical development and
clinical testing. More recently, the pressure has been
growing for pharmaceutical companies to develop pro-
cesses that are also environmentally friendly. In this
review, some of the opportunities and challenges this
presents for biocatalysis will be highlighted.
Rationale for introducing biocatalysis in
pharmaceutical syntheses
In recent years, process chemists in the pharmaceutical
industry have been turning their attention to the appli-
cation of biocatalysis using either isolated enzymes
or, more commonly, immobilized enzymes or whole-cell
Corresponding author: Woodley, J.M. (jw@kt.dtu.dk).
0167-7799/$ – see front matter ß 2008 Elsevier Ltd. All rights reserved. doi:10.1016/j.tibtech.2008.03.004 Available online 22 April 2008
catalysts. The exquisite selective properties of enzymes
mean that they can be used to resolve an existing chiral
center, such as kinetic resolution with a lipase, or, more
interestingly, to create new chiral centers via asymmetric
reactions, such as reduction with dehydrogenases or C-C
bond formation by lyases. Process chemists reason that
this provides an effective synthetic strategy for creating
optically pure molecules, which are essential for the man-
ufacture of many pharmaceutical compounds. The use of
enzymes for chemical synthesis in this context has several
advantages, including the avoidance of protection and de-
protection steps because enzymes are not only highly
selective but also operate under mild conditions. This
provides the possibility to drastically reduce the number
of process steps (i.e. ‘telescoping’ the process), thereby
reducing associated E-factors (Box 1). In particular, when
molecules with multiple chiral centers or molecules that
contain many functional groups are required, the use of
mild enzymatic catalysis often is able to provide a route
that avoids protection (and subsequent de-protection)
steps. Recognition of the benefits of selective biocatalysis
has resulted in the introduction of a significant number of
biocatalytic reactions into the synthetic strategies for
small-molecule intermediates and pharmaceuticals [1,2]
either already on the market or still in the development
pipeline. There are estimated to be around 150 imple-
mented biocatalytic processes in industry, and the majority
of these are in the pharmaceutical sector [3]. Although the
more widespread application of large-scale biocatalysis is
currently restricted because of the limited number of com-
mercially available synthetically useful enzymes and lim-
ited development speed, this approach is highly promising
because functionalized molecules of interest could be syn-
thesized with high regio- or stereo-selectivity. Asymmetric
reactions that are of interest for biocatalysis include those
listed in Table 1. To utilize these on a large scale, suitable
enzyme preparations will need to be made available. How-
ever, in cases where enzyme and process development was
possible, scalable synthetic routes have subsequently been
established. For example, Merck and Co. Inc. established a
biocatalytic process that used an enzymatic asymmetric
ketone reduction for the synthesis of (S)-3,5-bistrifluoro-
methylphenyl ethanol, an important alcohol intermediate
required for the synthesis of NK-1 receptor antagonists
[4]. Isolated alcohol dehydrogenase from Rhodococcus ery-
thropolis reduced the poorly water-soluble ketone with
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Review Trends in Biotechnology Vol.26 No.6

Box 1. E-factors [6]

 The E-factor is defined as the mass ratio of waste to product in a
given synthetic scheme.
 The E-factor is widely regarded as a very quick assessment of the
environmental compatibility of a process and frequently reflects
the complexity of the synthesis.
 Typical E-factors in industry:
- Bulk chemicals <0.1 kg waste/kg product
- Fine chemicals 5–50 kg waste/kg product
- Pharmaceutical processes 25–100 kg waste/kg product
excellent optical purity (ee of 99.9%) and conversion (98%).
The process was optimized, yielding product concen-
trations of up to 580 mM and space–time yields of up to
260 g/L/d (grams per liter per day) [4], clearly demonstrat-
ing the scalable potential of biocatalytic processes.
The trend for small-molecule therapeutics with increas-
ingly complex structures, which often contain several
chiral centers that need to be optically pure, is set to
continue in the future to increase the selectivity of
therapies and reduce unwanted side effects. The increas-
ing complexity, and therefore value, of the starting
material for many enzymatic reactions means that achiev-
ing high yields is becoming increasingly important. To
synthesize such compounds, the best available chemical
technology and catalysis will be required, and this is
expected to incorporate biocatalysis to an increasing extent
because of the increasing number of chiral centers and
functionality required. A criticism of many biocatalytic
syntheses has been that they suffer from a mere 50% yield
when racemic mixtures are being resolved. For the suc-
cessful application of biocatalysis in the future, the current
low yields will need to be overcome; this can be achieved
with the increased use of asymmetric enzymes, which are
able to provide a 100% yield (Table 1). For those reactions
in which the enzymatic resolution of enantiomers remains
the best possible route, the reported yields are now greater
than 50% in an increasing number of reactions because of
recycling of the unwanted enantiomer with chemical or
enzymatic deracemisation.

Table 1. Key asymmetric biocatalytic reactions [1]

Reaction Enzyme Type(s) of Product Number of
category reaction chiral centers
Oxidation Cytochrome Hydroxylation 1
P450

Dihydroxylation 2

Epoxidation 1 or 2

Monooxygenase Baeyer-Villiger 1

Haloperoxidase Epoxidation 1 or 2

Halohydrin 2
formation

Reduction Transaminase Transamination 1

Enoate Enolate 1
reductase reduction

Hydrolysis Epoxide Hydrolosis 2

hydrolase

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Review
Green credentials of biocatalysis
Most pharmaceutical manufacturing processes involve
long and complex syntheses that result in particularly high
E-factors [5,6] relative to other industrial sectors. By defi-
nition, low E-factors imply green processes, so methods of
lowering E-factors are of particular interest. Because bio-
catalysis is highly selective and, furthermore, able to avoid
protection steps, the total number of steps in a synthesis is
often reduced when biocatalytic steps are introduced, there-
fore significantly reducing the high E-factors. This is a clear
example of how biocatalysis contributes to the development
of green syntheses. Moreover, the introduction of biocata-
lysis is often associated with significant environmental
improvements and cost reductions that are harder to
quantify [5,7–9]. For example, ketone reductions currently
used in the large scale manufacture of a range of pharma-
ceuticals operate at ambient temperature and neutral pH in
an environmentally benign aqueous system. Furthermore,
the cofactors used in biocatalysis are non-toxic, thereby
producing only innocuous waste streams. These green cre-
dentials of biocatalysis (Box 2) have rarely been quantitat-
ively assessed, and there are only very few examples in the
literature of direct comparisons between chemical and bio-
catalytic routes. Nevertheless, the benefits of biocatalysis
listed in Box 2 are clearly advantageous from an environ-
mental point of view. Many pharmaceutical companies are
now aiming to manufacture their products as much as
possible in an environmentally friendly way because of
regulatory as well as consumer pressure. Biocatalysis could
be one technology (alongside other catalytic methods and
novel synthetic routes) that can assist in achieving this
objective. The driving force for changing already established
chemical processes is increased efficiency and greener pro-
cesses with biocatalysis. However, such a change is often
hard to justify from a business point of view, especially when
the remaining product patent lifetime is short. By contrast,
greater opportunities for biocatalysis therefore might arise
in the synthesis of new molecules that are currently in the
clinical pipeline.
Potential roles for biocatalysis in creating new green
chemical synthetic processes
To develop syntheses that are environmentally compatible,
improvements to existing processes are required as well as,
Box 2. Green credentials of biocatalysis
Biocatalysis:
 operates in water (thus replacing organic solvents)
 has highly selective catalysis, including regio- and stereo-
selectivity (thus reducing E-factors)
 operates in mild conditions, avoiding the need for protection (thus
reducing E-factors)
 overcomes the use of some hazardous materials (resulting in
improved LCA)
 uses renewable resources (resulting in improved LCA)
 can be modified, that is, the biocatalyst properties can be altered
to suit the process (thus improving the ease of processing)
 is rarely endo- or exo-thermic (thus reducing energy require-
ments)
 provides a high yield as a result of selectivity and mild conditions
(thus improving the efficiency of processing)
 is catalytic rather than stoichiometric (thus improving the ease of
processing)
Trends in Biotechnology Vol.26 No.6
and even more importantly, when new synthetic schemes
are implemented. Aside from a reduction in the E-factor of
a given synthesis process, biocatalysis can furthermore
contribute to the replacement of hazardous reagents and
commonly used organic solvents.
Replacement of hazardous reagents
The replacement of hazardous reagents with less harmful
alternatives is a major goal for green chemistry and bio-
catalysis. A good example of such an alternative is the
biocatalytic reduction of amides to amines, which avoids
the use of potentially hazardous hydride reagents. The
synthesis of amines is an essential requirement in vir-
tually all small-molecule pharmaceutical syntheses. A
common route to the synthesis of amines is amide
reduction via the use of hydrides such as LiAlH4 (lithium
aluminium hydride) or DIBAL (diisobutylaluminium
hydride). However, there are significant safety concerns
regarding the large-scale use of these compounds due to
their corrosive and hazardous nature. Alternatives for
amide reduction are therefore particularly sought after
in the implementation of new synthetic schemes. From a
theoretical standpoint, hydrogen would be the ideal reduc-
tant because only water is formed as a by-product. How-
ever, the traditional catalysts for this hydrogen reaction
require high temperature and operation under high pres-
sure, which, in addition to an increased energy require-
ment, leads to a loss of selectivity for sensitive compounds.
Biocatalytic routes would provide an important alternative
pathway under mild conditions, such as ambient tempera-
ture and pressure. Sources for the enzymes that might
carry out such a reaction can be found in many microor-
ganisms. However, in most microorganisms, the preferred
path is to oxidize the amide, which often includes amide
hydrolysis in the metabolism, leading to an unwanted side
reaction. Interestingly, switching to an anaerobic environ-
ment makes amide reduction possible, and this strategy
has recently been used with a strain of Clostridium spor-
ogenes that was able to reduce benzamide to benzylamine
with yields of up to 73% [10]. This preliminary study also
reported side activities that reduced the yield at high
substrate concentration, but this limitation might be over-
come by using isolated enzymes instead of the whole-cell
biocatalysts.
A second example of a reaction with considerable safety
concerns is oxidation, which is an important reaction in
chemical and pharmaceutical syntheses. Significant
improvements have been made in this area in recent years,
which has resulted in the availability of far greener
oxidation reagents. For example, processes have been
developed that use TEMPO (2,2,6,6-tetramethylpiperi-
dine-1-oxyl), NaOCl (sodium hypochlorite) or Pd (palla-
dium) instead of the previously required high-valent
metals, which were also required in stoichiometric rather
than in small catalytic amounts. Despite these improve-
ments, many of the catalytic oxidations still need to be
conducted in halogenated solvents and require the removal
or recycling of catalysts containing heavy metals. As an
alternative to the above mentioned oxidizing reagents,
oxygen would be ideal. However, in the presence of organic
solvents, which remain the preferred medium to date,
323
Review
it incurs significant safety concerns. Nevertheless,
biocatalytic oxidations can be carried out by oxidizing
enzymes [11] in an aqueous environment with oxygen that
is usually supplied as air. One class of such enzymes is the
chloroperoxidases (CPOs). For example, the CPO from
Caldariomyces fumago has been shown to function effec-
tively as an oxidation biocatalyst with resulting high yields
and selectivities. However, for industrial implementation,
improvements in the enzyme are required because CPO (a
heme-dependent peroxidase) is not very stable and is
sensitive to high concentrations of its substrate hydrogen
peroxide. Another potentially interesting biocatalyst is the
enzyme cyclohexanone monooxygenase, which is able to
catalyse the well known Baeyer-Villiger oxidation, in-
cluding the insertion of an oxygen into a cyclic ketone to
create a lactone [12]. This enzyme has been particularly
successful in catalyzing the synthesis of multi-cyclic lac-
tones for potential use as pharmaceutical intermediates
with high regio- and stereo-selectivity. A remaining prac-
tical problem for the industrial application of this and
many other enzymes is successful biocatalysis at high
substrate concentration, which will require detailed
knowledge of process methods, such as substrate feeding
and product removal, for the achievement of high yields. A
third class of interesting biocatalysts for oxidation reac-
tions, the laccasses, has been successfully used for oxi-
dation of functional groups, such as the coupling of phenols
and steroids and the creation of C-N bonds. Laccasses
operate under slightly acidic conditions (pH 4.5) at room
temperature and importantly can achieve product concen-
trations of up to 100 g/L [13]. Finally, lipases have been
shown to use peroxides to catalyse epoxide formation
[14,15]. Lipases are the most widely used enzymes in
organic synthesis and will readily catalyze a range of
reactions, such as hydrolysis, transesterification and ester-
ification. They can also be used to synthesize peroxy car-
boxylic acids from hydrogen peroxide and free carboxylic
acid, and they are ultimately able to provide a clean route
to epoxides as potential intermediates to a range of chemi-
cals and pharmaceuticals.
Replacement of organic solvents in reactions
Organic solvent use accounts for around 80% of mass
utilization in typical pharmaceutical and fine chemical
synthetic processes. In addition, many organic solvents
are toxic and therefore, on a mass basis, account for the
largest proportion of chemicals of concern used in any
industrial synthetic scheme. In the laboratory, synthesis
chemists use organic solvents to assist in solubilizing
compounds; these solvents increase the compounds’ avail-
ability for chemical reagents and catalysts. Upon indus-
trial scale-up, many of these solvents will lead to
considerable safety concerns or difficulties for effective
product recovery. The large number of steps in pharma-
ceutical syntheses mean that intermediate solvent extrac-
tion results, for example, in a large inventory of organic
solvent. Hence, alternatives are being sought that can
overcome these problems; for example, GlaxoSmithKline
has recently taken two approaches to select solvents more
suitable for scale-up [16]. The first approach is to investi-
gate options for replacing organic solvents with more
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Trends in Biotechnology Vol.26 No.6
environmentally compatible solvents, such as water. Most
biological processes and enzymatic reactions take place in
water, and therefore biocatalysis is likely to be considered.
In some reactions, two-phase biocatalytic systems can be
used to partially replace solvent, as well as to facilitate
substrate supply [17] or product removal [18]. This is well
illustrated for asymmetric ketone reductions, and several
conversions have been carried out in enzymatic two-phase
systems. For example, using alcohol dehydrogenase from
R. erythropolis, p-chloroacetophenone was converted into
the optically active s-enantiomer with high optical purity
(ee >99%) and conversion (69%) in a two-phase system that
was composed of water and a long chain alkane [19]. The
choice of the organic solvent in the two-phase system is
crucial to ensure sufficient biocatalyst activity and
stability. It is important to note that non-enzymatic chemi-
cal reactions are also increasingly being carried out in
water [20]. This is an important step towards the devel-
opment of greener chemo-enzymatic synthetic routes [21].
The second approach is to select the solvent in a systematic
manner based on the solvent properties, including those
which assist in the development of an environmentally
compatible process [22]. Solvent selection incorporating
green issues in a quantifiable way will not only lead to
improved safety and potentially a greener reaction but
also, critically, will improve product recovery downstream
of the reactor. Computer-based algorithms are now becom-
ing available that will make systematic solvent selection
procedures more automated [23,24], and this should enable
the consideration of green alternatives at an early stage in
process development, when retro-synthetic schemes are
drawn up.
Challenges for implementing green biocatalytic
processes
Downstream processing
Nature has evolved enzymes to operate at low concen-
trations of substrates and hence products. The low con-
centrations are far from those required in industrial
processes and place a particular burden on downstream
processing. Because most enzymes catalyze reactions in an
aqueous medium, the reaction itself is safe and scalable.
However, this also means that product recovery might be
difficult because large quantities of water need to be
removed, and this has significant economic implications
in large-scale processes. Consequently, in many pharma-
ceutical manufacturing processes, liquid–liquid extraction
is a frequently required step in the downstream process.
This represents a challenge for the implementation of
green processes because of the introduction of organic
solvents. Alternative solutions are becoming available that
involve multi-phasic reaction media or in situ product
removal [25].
Systematic evaluation of processes
The development of new medicines is an extremely cost-
intensive process that includes the formulation of the final
drug form and the extensive testing of processes at each
stage. However, the synthesis of the therapeutic molecules
themselves is also of great importance and is often over-
looked when new therapies are discussed. To recover the
Review
Box 3. Research areas with potential for green chemistry
[33]
 Amide formation avoiding poor atom economy reagents
 Reduction of amides without hydride reagents
 Oxidation and epoxidation methods without the use of chlori-
nated solvents
 Replacement of organic-solvent-based reactions
huge investment costs for drug discovery and development,
drug compounds have to be manufactured efficiently as
well as economically and, most importantly, to standards
that allow for their safe and effective use. Furthermore,
manufacturing processes in the drug sector need to be
developed rapidly to capitalize upon patent protection
Figure 1. Two alternative routes to 7-aminocephalospric acid (7-ACA). Both routes start from the potassium salt of cephalosporin (a) and result in the synthesis of 7-ACA
(b). Further details of these routes can be obtained from [32].
Trends in Biotechnology Vol.26 No.6
(see Box 3). The large attrition rate of new molecules
and an inevitable rush through early stages of process
and product development might have the consequence that
novel strategies for process chemistry or engineering are
considered too late to be incorporated, resulting in a con-
servative approach to new technology [26]. Therefore,
potential routes to new products, including greener routes,
might be missed by industry, whether or not they might
involve biocatalysis. Any systematic approach that quan-
titatively identifies potential improvements can therefore
be a great help in enhancing development speed. Several
companies have implemented a so-called green ‘score card’
to help them develop greener processes. The systematic
nature of this approach also helps in rapid process de-
velopment and decision-making. At GlaxoSmithKline, the
325
 Review
Table 2. Qualitative comparison of chemical and biocatalytic
routes to 7-ACA
Route Environmental Energy Safety Process
impact use implications efficiency
Chemical
Enzymatic
Details of routes are given in Figure 1 and reference [32]. Adapted, with permission,
from Ref. [32]. The routes are identified as being advantageous ( ), disadvanta-
geous ( ) or having no difference ( ).
green score card now involves the incorporation of unit
operation analysis as well as life cycle analysis (LCA)
concepts for each process. Several measures are therefore
used to assess a given route. A software tool (known as
FLASCTM) enables the quantification of these environmen-
tal measures, although, rather interestingly, weighting is
not applied to a given measure so that a flexible system for
route evaluation and comparison can be built [27–31]. One
of the few direct comparisons on environmental grounds of
a biocatalytic and chemical route for pharmaceutical syn-
thesis (production of 7-ACA – Figure 1) was recently
created by using this software [32]. The outcomes regard-
ing energy, environment and safety are outlined in Table 2
and show that, in this case, the choice of the enzymatic
route can be justified from an environmental standpoint. A
greater number of such comparative evaluations are
required so that a database of parameters for biocatalytic
and chemical processes can be built to help process engin-
eers and chemists to find replacement routes or to establish
new synthetic strategies.
Industrial perspectives
A most interesting development in 2007 was the pro-
gression of an open dialogue under the auspices of the
Green Chemistry Institute (ACS) within the pharmaceu-
tical industry. This initiative currently involves AstraZe-
neca, Eli Lilly and Co., GlaxoSmithKline, Johnson and
Johnson, Merck and Co. Inc., Pfizer Inc. and Schering-
Plough Corp. and has resulted in the publication of a report
that addressed the green chemistry agenda [33]. This
dialogue provides a forum to identify reactions that, from
an environmental viewpoint, would benefit from better
synthetic schemes, including but not restricted to biocata-
lysis. Several areas are now the subject of intensive
research efforts focused on improved syntheses, and what
is perhaps more significant is that there is considerable
agreement amongst the pharmaceutical companies
involved on what these targets should be (see Box 3). That
such an extensive dialogue is taking place reflects the
seriousness with which this issue is being taken by indus-
try, making this forum a most promising approach for a
wider implementation of green chemistry.
Conclusions
This review has identified several targets where enzyme-
based processes will have an important role in developing
greener synthetic methods for the pharmaceutical indus-
try. With regard to a more widespread use of biocatalytic
processes, several important challenges remain. Specifi-
cally, for biocatalytic processes we can conclude:
 Biocatalytic routes, or parts of routes, identified in
synthetic processes need to be evaluated alongside
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Trends in Biotechnology Vol.26 No.6
existing possibilities. Important tools, such as LCA and
other evaluation methods, are being established, but
further case studies are required.
 Synthesis of new compounds via greener routes is a
significant opportunity for biocatalysis, but it will need
to be accompanied by the establishment of rapid process
development methods [34].
 The limiting factors in most enzymatic methods are not
factors in the chemistry itself, but rather the substrate
repertoire, enzyme availability and enzyme stability.
There is little doubt that modern biological tools, such as
protein engineering and directed evolution [35], will
play an important role in overcoming these limitations.
 A further challenge is downstream processing, where
effective techniques need to be devised to recover
products in high concentrations from aqueous streams.
Some solutions are available, but more work is required
to overcome this obstacle.
 Early evaluation of environmental impact of industrial
processes will avoid later complications, and this is true
for any type of synthetic route [36].
In the coming years we can expect an increased presence
of biocatalysis in small-molecule pharmaceutical synth-
eses [2], and this will potentially bring significant environ-
mental improvements to these processes.
Acknowledgements
The author would like to thank Stuart R. Tindal (Technical University of
Denmark), Richard K. Henderson, Concepción Jiménez-González and
Chris Preston (GlaxoSmithKline) for stimulating discussions during the
writing of this manuscript.
References
1 Pollard, D.J. and Woodley, J.M. (2007) Biocatalysis for pharmaceutical
intermediates: the future is now. Trends Biotechnol. 25, 66–73
2 Schoemaker, H.E. et al. (2003) Dispelling the myths – biocatalysis
industrial synthesis. Science 299, 1694–1697
3 Panke, S. and Wubbolts, M. (2005) Advances in biocatalytic synthesis of
pharmaceutical intermediates. Curr. Opin. Chem. Biol. 9, 188–194
4 Pollard, D.J. et al. (2006) Effective synthesis of (S)-3,5-
bistrifluoromethylphenyl ethanol by asymmetric enzymatic
reduction. Tetrahedron Asymmetry 17, 554–559
5 Sheldon, R.A. (1994) Consider the environmental quotient. Chemtech
24, 38–47
6 Sheldon, R.A. (2007) The E factor: fifteen years on. Green Chem. 9,
1273–1283
7 Bull, A.T. et al. (1999) Biocatalysts for clean industrial products and
processes. Curr. Opin. Microbiol. 2, 246–251
8 Rozzell, J.D. (1999) Commercial scale biocatalysis: myths and realities.
Bioorg. Med. Chem. 7, 2253–2261
9 Hatti-Kaul, R. et al. (2007) Industrial biotechnology for the production
of bio-based chemicals – a cradle-to-grave perspective. Trends
Biotechnol. 25, 119–124
10 Dipeolu, O. et al. (2005) Biocatalytic amide reduction using Clostridium
sporogenes. Biotechnol. Lett. 27, 1803–1807
11 Burton, S.G. (2003) Oxidizing enzymes as biocatalysts. Trends
Biotechnol. 21, 543–549
12 Mihovilovic, M.D. (2006) Enzyme mediated Baeyer-Villiger oxidations.
Curr. Org. Chem. 10, 1265–1287
13 Wells, A. et al. (2006) Green oxidations with laccase-mediator systems.
Biochem. Soc. Trans. 34, 304–308
14 Bjorkling, F. et al. (1992) Lipase catalysed synthesis of
peroxycarboxylic acids and lipase mediated oxidations. Tetrahedron
48, 4587–4592
15 Ankudey, E.G. et al. (2006) Lipase-mediated epoxidation
utilizing urea-hydrogen peroxide in ethyl acetate. Green Chem. 8,
923–926
Review Trends in Biotechnology Vol.26 No.6

16 Constable, D.J.C. et al. (2007) Perspective on solvent use in the
pharmaceutical industry. Org. Process Res. Dev. 11, 133–137
17 Kim, P-Y. et al. (2007) Substrate supply for effective biocatalysis.
Biotechnol. Prog. 23, 74–82
18 Stark, D. and von Stockar, U. (2003) In-situ product removal (ISPR) in
whole-cell biotechnology during the last 20 years. Adv. Biochem. Eng.
Biotechnol. 80, 149–175
19 Groger, H. et al. (2003) Practical asymmetric enzymatic reduction
through discovery of a dehydrogenase – compatible biphasic reaction
media. Org. Lett. 5, 173–176
20 Hailes, H.C. (2007) Reaction solvent selection: the potential of water as
a solvent for organic transformations. Org. Process Res. Dev. 11, 114–
120
21 Hailes, H.C. et al. (2007) Integration of biocatalytic conversions into
chemical syntheses. J. Chem. Technol. Biotechnol. 82, 1063–1066
22 Jiménez-González, C. et al. (2005) Expanding GSK’s solvent selection
guide – application of life cycle assessment to enhance solvent
selections. Clean Technol. Environ. Policy 7, 42–50
23 Gani, R. et al. (2005) Method for selection of solvents for promotion of
organic reactions. Comput. Chem. Eng. 29, 1661–1676
24 Gani, R. et al. (2006) A modern approach to solvent selection. Chem.
Eng. 113, 30–43
25 Woodley, J.M. et al. (2008) Future directions for in-situ product
removal (ISPR). J. Chem. Technol. Biotechnol. 83, 121–123
26 Pisano, G. (1996) The Development Factory, Unlocking the Potential of
Process Innovation, Harvard Business School Press
27 Constable, D.J.C. et al. (2001) Green chemistry measures for process
research and development. Green Chem. 3, 7–9
28 Jiménez-González, C. et al. (2001) How do you select the ‘greenest’
technology? Development of guidance for the pharmaceutical industry.
Clean Prod. Process 3, 35–41
29 Curzons, A.D. et al. (2001) So you think your process is green, how do
you know? Using principles of sustainability to determine what is
green – a corporate perspective. Green Chem. 3, 1–6
30 Jiménez-González, C. et al. (2002) Developing GSK’s green technology
guidance: methodology for case-scenario comparison of technologies.
Clean Technol. Environ. Policy 4, 44–53
31 Curzons, A. et al. (2007) Fast life-cycle assessment of synthetic chemistry
tool, FLASCTM tool. Int. J. Life Cycle Assessment 12, 272–280
32 Henderson, R.K. et al. EHS and LCA assessment of 7-ACA synthesis: a
case study for comparing biocatalytic and chemical synthesis.Plz
update reference [32]. Ind. Biotechnol. (in press)
33 Constable, D.J.C. et al. (2007) Key green chemistry research areas – a
perspective from pharmaceutical manufacturers. Green Chem. 9, 411–
420
34 Lye, G.J. et al. (2003) Accelerated design of bioconversion processes
using automated microscale processing techniques. Trends Biotechnol.
21, 29–37
35 Hibbert, E.G. et al. (2005) Directed evolution of biocatalytic processes.
Biomol. Eng. 22, 11–19
36 Tucker, J.L. (2006) Green chemistry, a pharmaceutical perspective.
Org. Process Res. Dev. 10, 315–319

Elsevier celebrates two anniversaries with

a gift to university libraries in the developing world
In 1580, the Elzevir family began their printing and bookselling business in the Netherlands, publishing
works by scholars such as John Locke, Galileo Galilei and Hugo Grotius. On 4 March 1880, Jacobus
George Robbers founded the modern Elsevier company intending, just like the original Elzevir family, to
reproduce fine editions of literary classics for the edification of others who shared his passion, other
‘Elzevirians’. Robbers co-opted the Elzevir family printer’s mark, stamping the new Elsevier products
with a classic symbol of the symbiotic relationship between publisher and scholar. Elsevier has since
become a leader in the dissemination of scientific, technical and medical (STM) information, building a
reputation for excellence in publishing, new product innovation and commitment to its STM
communities.

In celebration of the House of Elzevir’s 425th anniversary and the 125th anniversary of the modern
Elsevier company, Elsevier donated books to ten university libraries in the developing world. Entitled
‘A Book in Your Name’, each of the 6700 Elsevier employees worldwide was invited to select one of
the chosen libraries to receive a book donated by Elsevier. The core gift collection contains the
company’s most important and widely used STM publications, including Gray’s Anatomy, Dorland’s
Illustrated Medical Dictionary, Essential Medical Physiology, Cecil Essentials of Medicine, Mosby’s
Medical, Nursing and Allied Health Dictionary, The Vaccine Book, Fundamentals of Neuroscience, and
Myles Textbook for Midwives.

The ten beneficiary libraries are located in Africa, South America and Asia. They include the Library of
the Sciences of the University of Sierra Leone; the library of the Muhimbili University College of Health
Sciences of the University of Dar es Salaam, Tanzania; the library of the College of Medicine of the
University of Malawi; and the University of Zambia; Universite du Mali; Universidade Eduardo
Mondlane, Mozambique; Makerere University, Uganda; Universidad San Francisco de Quito, Ecuador;
Universidad Francisco Marroquin, Guatemala; and the National Centre for Scientific and Technological
Information (NACESTI), Vietnam.

Through ‘A Book in Your Name’, these libraries received books with a total retail value of
approximately one million US dollars.

For more information, visit www.elsevier.com

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