Available online at www.sciencedirect.com Biocatalysis — key to sustainable industrial chemistry Roland Wohlgemuth The ongoing trends to process improvements, cost reductions and increasing quality, safety, health and environment requirements of industrial chemical transformations have strengthened the translation of global biocatalysis research work into industrial applications. One focus has been on biocatalytic single-step reactions with one or two substrates, the identification of bottlenecks and molecular as well as engineering approaches to overcome these bottlenecks. Robust industrial procedures have been established along classes of biocatalytic single-step reactions. Multi-step reactions and multi-component reactions (MCRs) enable a bottom-up approach with biocatalytic reactions working together in one compartment and recations hindering each other within different compartments or steps. The understanding of the catalytic functions of known and new enzymes is key for the development of new sustainable chemical transformations. Address Sigma–Aldrich, Industriestrasse 25, CH-9470 Buchs, Switzerland Corresponding author: Wohlgemuth, Roland ([email protected]) Current Opinion in Biotechnology 2010, 21:713–724 This review comes from a themed issue on Chemical biotechnology Edited by Phil Holliger and Karl Erich Jaeger Available online 26th October 2010 0958-1669/$ – see front matter # 2010 Elsevier Ltd. All rights reserved. DOI 10.1016/j.copbio.2010.09.016 Introduction The creation of value-added products by chemical trans- formations has contributed significantly to the quality of life over the centuries and has reached a high level, but it has been suggested that many of the stoichiometric reactions in current use should be replaced by catalytic processes [1]. Although catalytic tools are not only a cornerstone of our present economy and society, but also a key feature of basic life processes, most of the catalysts used in the automotive, fuel refining, and chemical industries consist either of inorganic, organometallic or of organic catalysts in heterogeneous form, as for example, catalysts involved in pollutant removal from the exhaust leaving the car engines. The use of biocata- lysts in chemical transformations has really taken off with the focus on safe, healthy, resource efficient and econ- omical, energy saving, and environment-friendly pro- duction procedures. The global needs for clean manufacturing technologies, nonrenewable raw materials, management of hazardous chemicals and waste present new research challenges to both chemistry and biotech- nology. These sciences are taking up these challenges and the initiatives in Green/sustainable chemistry [2,3] and white/industrial biotechnology [4] have emerged in their disciplines independently. It is therefore of crucial importance for the success of implementation and trans- lation of science and technology into standard industrial practice to develop a common chemistry–biotechnology interface. One common opportunity for improvement and invention is the current use of protecting groups for overcoming nonselective and incompatible reactivities in synthesis and biomimetic as well as enzyme-catalyzed synthesis can provide the selectivities needed to over- come barriers [5]. The manufacturing of molecular com- plexity from simple starting materials with a minimum number of steps, avoiding protection–deprotection loops and orientation towards function of the product attract much interest and biocatalytic process steps are well positioned for contributing to the solutions of the above-mentioned challenges [6]. The creation of sustainable value by viable industrial processes and synthetic pathways requires not only research progress in chemistry and biotechnology, but in addition the integration of research from molecular and engineering sciences, thereby enabling a large range of industrial biotransformations [7–10]. As reaction devel- opment serves different practical needs, progress in the working areas single-step reactions, multi-step reactions, and multi-component reactions (MCRs) will be discussed in the following sections. Despite the enormous achieve- ments in the chemical synthesis of organic compounds, once believed to be accessible only by biological pro- cesses and ‘vital forces’, over the past two centuries, many present state-of-the-art processes are highly inefficient [3]. This and additional boundary conditions like safety, health and environment issues in industrial processes have revitalized the interest in the discovery/invention of novel biocatalytic reactions and reaction method- ologies, which have been evolved by nature to achieve highly efficient and selective transformations. Therefore the section on the development of new biocatalytic reaction methodology addresses this important industrial innovation area. Industrial biocatalytic single-step reactions The early success of single biocatalytic reaction steps in classical organic synthesis schemes has led to an www.sciencedirect.com Current Opinion in Biotechnology 2010, 21:713–724
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Available online at www.sciencedirect.com
Biocatalysis — key to sustainable industrial chemistryRoland Wohlgemuth
The ongoing trends to process improvements, cost reductions
and increasing quality, safety, health and environment
requirements of industrial chemical transformations have
strengthened the translation of global biocatalysis research
work into industrial applications. One focus has been on
biocatalytic single-step reactions with one or two substrates,
the identification of bottlenecks and molecular as well as
engineering approaches to overcome these bottlenecks.
Robust industrial procedures have been established along
classes of biocatalytic single-step reactions. Multi-step
reactions and multi-component reactions (MCRs) enable a
bottom-up approach with biocatalytic reactions working
together in one compartment and recations hindering each
other within different compartments or steps. The
understanding of the catalytic functions of known and new
enzymes is key for the development of new sustainable
of heavy metals, cost reductions and avoiding specialized
high-pressure hydrogenation equipment have been found
as specific advantages of the biocatalytic process [26��].
Glycosylation reactions
As selective chemical glycosylation reactions require a
substantial synthetic effort involving various protecting
group chemistries in organic solvents, the use of glyco-
syltransferases for coupling glycosyl donors to nonpro-
tected acceptors in aqueous media (Figure 3) continues to
attract a lot of interest [27–29]. Methods based on the
application of glycosyltransferases are currently recog-
nized as being the most effective for the preparation of
complex and highly pure oligosaccharides [30�]. The
trihexosylceramides Gb3 and iGb3 have been synthes-
ized by specific galactosyltransferases using lactosylcer-
amide as acceptor [31]. Sialyltransferases have been used
in chemoenzymatic or whole-cell approaches for the
synthesis of a large library of sialoside standards and
derivatives [32�]. Carbohydrate-based drug design makes
use of various glycosyltransferases for the production of
novel glycosylated compounds, as no single universal
glycosyltransferase has been found [33]. The final hexose
to be transferred from the NDP-hexose to the aglycon can
thereby be diversified by a variety of enzymes like
dehydratases, epimerases and aminotransferases.
Hydrolysis and reverse hydrolysis reactions
On the basis of the vast number of established enzymatic
reactions using hydrolases in aqueous and nonaqueous
systems, this area has become well established and new
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Sustainable industrial chemistry Wohlgemuth 715
Figure 1
Selected biocatalytic oxidation and reduction reactions. The cyclohexanone-monooxygenase-catalyzed Baeyer–Villiger oxidation of bicycloheptenone
has been applied industrially by Sigma–Aldrich with the substrate-feed-product-recovery-technology (SFPR) using Optipore L-493 as adsorber for
high space-time yield [14�].
applications appearing in various fields of organic chem-
istry can build on this experience (Figure 4). The large-
scale availability of many hydrolases like acylases,
amidases, esterases, lipases, proteases and their ease of
use without any cofactors has been a key factor for the
rapid growth of this reaction class in industry [34]. The
robustness and scalability of these reactions with stan-
dard equipment have been useful for resolutions, dera-
cemizations, desymmetrizations in early steps or mild
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deprotections in late steps of a synthesis. The complete
conversion of a substrate into one product of high enan-
tiomeric purity is particularly attractive, as for example,
in desymmetrizations of prochiral diols or diesters. Inex-
pensive acyl donors like acids or simple esters are pre-
ferred for cost-sensitive productions, but require tools to
drive reactions to completion. Lipase-catalyzed acyla-
tions with activated acyl donors like enol esters and acid
anhydrides are practically irreversible. Lipase-catalyzed
Current Opinion in Biotechnology 2010, 21:713–724
716 Chemical biotechnology
Figure 2
Selected biocatalytic amination reactions. The transaminase-catalyzed asymmetric amination of prositagliptin ketone to sitagliptin has been applied
industrially by Merck. Abbreviations: PLP = pyridoxal-50-phosphate; MBA = (S)-a-methylbenzylamine.
polymerization in an organic solvent or one bulk mono-
mer is advantageous in reducing energy consumption and
in polymerizing multifunctional monomers or monomers
which undergo side reactions or are degraded under
process conditions [35]. The enzymatic resolution of a
substrate with a remote stereogenic center has been
realized in the first enantioselective synthesis of (S)-
monastrol [36]. An interesting high yield synthesis of
12-aminolauric acid from v-laurolactam has been devel-
oped by enzymatic transcrystallization using v-laurolac-
tam hydrolase from Acidivorax sp. [37�]. This method has
been chosen because of low conversion ratios by the use
of organic solvents and biphasic systems. Enzymatic
Current Opinion in Biotechnology 2010, 21:713–724
transcrystallization starts with the addition of crystalline
substrate to the aqueous reaction medium, which dis-
solves the substrate up to its solubility limit, and the
enzymatic reaction can then give the soluble product,
which will crystallize, when the product concentration
from the enzymatic conversion exceeds the product
solubility. Overall, the process resembles a SFPR system
[11], where the crystalline substrate is converted into
crystalline product in a highly efficient and environment-
friendly process without organic solvent, acid or alkali. A
nitrilase-catalyzed kinetic resolution of 2-cyano-1,4-ben-
zodioxane and 2-cyano-6-formyl-1,4-benzodioxane to
optically active 1,4-benzodioxane-2-carboxylic acids
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Sustainable industrial chemistry Wohlgemuth 717
Figure 3
Selected biocatalytic glycosylation reactions representing the enormous potential of glycosyltransferases for future industrial applications.
enables mild and enantioselective nitrile hydrolysis
without damage to labile functional groups like the
formyl group [38].
Carbon–carbon formation reactions and carbon–carbon
bond cleaving reactions
The formation and cleavage of carbon–carbon bonds is of
prime importance for constructing the carbon skeleton
not only in synthetic organic chemistry, but also in the
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metabolic pathways of living cells. Among the great
variety of enzymes, hydroxynitrile lyases, aldolases,
and transketolases have attracted much interest
(Figure 5). Hydroxynitrile lyases have been valuable
for manufacturing enantiopure target cyanohydrins from
aldehydes, as versatile bifunctional building blocks for
chemical synthesis [39]. Strategies for overcoming reac-
tion limitations and suppression of nonenzymatic side
reactions combine approaches from enzyme and reaction
Current Opinion in Biotechnology 2010, 21:713–724
718 Chemical biotechnology
Figure 4
Selected biocatalytic hydrolysis and reverse hydrolysis reactions. A recombinant novel isoform of pig liver esterase termed alternative pig liver esterase
(APLE) has been applied industrially by DSM.
engineering [40]. Crude hydroxynitrile lyase has also
been used for the enantioselective cyanohydrin synthesis
in a microreactor [41]. Biocatalysis by means of aldolases
offers a unique stereoselective and green tool to perform
carbon–carbon bond formation or cleavage. Recent
advances in aldolase-catalyzed stereoselective carbon–carbon bond formation reactions are valuable for gener-
ating molecular diversity and for synthetic improvements
from small chiral polyfunctional molecules to highly
2. Clark JH: Chemistry goes green. Nat Chem 2009, 1:12-13.
3. Li CJ, Trost BM: Green chemistry for chemical synthesis. ProcNatl Acad Sci 2008, 105:13197-13202.
4. Wohlgemuth R: The locks and keys to industrial biotechnology.New Biotechnol 2009, 25:204-213.
5. Young IS, Baran PS: Protecting-group-free synthesis as anopportunity for invention. Nat Chem 2009, 1:193-205.
6. Wender PA, Miller BL: Synthesis at the molecular frontier.Nature 2009, 460:197-201.
7. Fessner WD, Anthonsen T (Eds): Modern Biocatalysis. Weinheim:Wiley-VCH; 2009.
8. Gotor V, Alfonso I, Garcia-Urdales E (Eds): Asymmetric OrganicSynthesis with Enzymes. Weinheim: Wiley-VCH; 2008.
9. Franssen MCR, Kircher M, Wohlgemuth R: Industrialbiotechnology in the chemical and pharmaceutical industries.In Industrial Biotechnology, Sustainable Growth and EconomicSuccess. Edited by Soetaert W, Vandamme EJ. Weinheim: Wiley-VCH; 2010.
10. Ghisalba O, Meyer HP, Wohlgemuth R: Industrialbiotransformation. In Encyclopedia of Industrial Biotechnology.Edited by Flickinger MC. Hoboken, NJ: Wiley; 2010.
11. Alphand V, Wohlgemuth R: Applications of Baeyer–Villigermonooxygenases in organic synthesis. Curr Org Chem 2010,14:1928-1965.
12. Hilker I, Gutierrez MC, Furstoss R, Ward J, Wohlgemuth R,Alphand V: Preparative scale Baeyer–Villiger biooxidation athigh concentration using recombinant Escherichia coli and insitu substrate feeding and product removal process. NatProtoc 2008, 3:546-554.
Current Opinion in Biotechnology 2010, 21:713–724
13. Torres Pazmino DE, Dudek HM, Fraaije MW: Baeyer–Villigermonooxygenases: recent advances and future challenges.Curr Opin Chem Biol 2010, 14:138-144.
14.�
Wohlgemuth R, Woodley JM: Asymmetric Baeyer–Villigerreactions using whole-cell biocatalysts. In Large-scaleAsymmetric Catalysis. Edited by Blaser HU, Federsel HJ.Weinheim: Wiley-VCH; 2010.
A summary of the first large-scale biocatalytic Baeyer–Villiger oxidationsand the bottlenecks that have been overcome.
15. Richter N, Neumann M, Liese A, Wohlgemuth R, Eggert T,Hummel W: Characterisation of a recombinant NADP-dependent glycerol dehydrogenase from gluconobacteroxydans and its application in the production of L-glyceraldehyde. ChemBioChem 2009, 10:1888-1896.
16. Richter N, Neumann M, Liese A, Wohlgemuth R, Weckbecker A,Eggert T, Hummel W: Characterization of a whole-cellcatalyst co-expressing glycerol dehydrogenase andglucose dehydrogenase and its application in thesynthesis of L-glyceraldehyde. Biotechnol Bioeng 2010,106:541-552.
18. Hall M, Stueckler C, Hauer B, Stuermer R, Friedrich T, Breuer M,Kroutil W, Faber K: Asymmetric bioreduction of activated C Cbonds using Zymomonas mobilis NCR enoate reductase andold yellow enzymes OYE 1–3 from yeasts. Eur J Org Chem 2008,9:1511-1516.
19. Fryszkowska A, Toogood H, Sakuma M, Gardiner JM,Stephens GM, Scrutton NS: Asymmetric reduction of activatedalkenes by pentaerythritol tetranitrate reductase: specificityand control of stereochemical outcome by reactionoptimisation. Adv Synth Catal 2009, 351:2976-2990.
20. Kosjek B, Fleitz FJ, Dormer PG, Kuethe JT, Devine PN:Asymmetric bioreduction of a,b-unsaturated nitriles andketones. Tetrahedron: Asymmetry 2008, 19:1403-1406.
21. Hohne M, Bornscheuer UT: Biocatalytic routes to opticallyactive amines. ChemCatChem 2009, 1:1-11.
22. Zhu D, Hua L: Biocatalytic asymmetric amination of carbonylfunctional groups — a synthetic biology approach to organicchemistry. Biotechnol J 2009, 4:1420-1431.
23. Koszelewski D, Tauber K, Faber K, Kroutil W: v-Transaminasesfor the synthesis of non-racemic a-chiral primary amines.Trends Biotechnol 2010, 28:324-332.
25. Schell U, Wohlgemuth R, Ward JM: Synthesis of pyridoxamine50-phosphate using an MBA: pyruvate transaminase asbiocatalyst. J Mol Catal B: Enzym 2009, 59:279-285.
26.��
Savile CK, Janey JM, Mundorff EC, Morre JC, Tam S, Jarvis WR,Colbeck JC, Krebber A, Fleitz FJ, Brands J et al.: Biocatalyticasymmetric synthesis of chiral amines from ketones appliedto sitagliptin manufacture. Science 2010, 329:305-309.
A variety of enzyme engineering techniques have been applied to thecreation of a transaminase biocatalyst with the required properties andactivity toward the prositagliptin ketone. This has resulted in an efficientbiocatalytic trans-amination process to replace a rhodium-catalyzedasymmetric hydrogenation for the large-scale manufacturing of the anti-diabetic compound sitagliptin.
27. Chokhawala HA, Huang S, Lau K, Yu H, Cheng J, Thon V, Hurtado-Ziola N, Guerrero JA, Varki A, Chen X: Combinatorialchemoenzymatic synthesis and high-throughput screening ofsialosides. ACS Chem Biol 2008, 3:567-576.
28. Wohlgemuth R: Tools and ingredients for the biocatalyticsynthesis of carbohydrates and glycoconjugates. BiocatalBiotransformation 2008, 26:42-48.
Review on the effective application of glycosyltransferases for the pre-paration of complex and highly pure oligosaccharides.
31. Adlercreutz D, Weadge JT, Petersen BO, Duus JØ, Dovichi NJ,Palcic MM: Enzymatic synthesis of Gb3 and iGb3 ceramides.Carbohydr Res 2010, 345:384-388.
32.�
Chen X, Varki A: Advances in the biology and chemistry of sialicacids. ACS Chem Biol 2010, 5:163-176.
A sialic acid review including recent advances in chemoenzymatic synth-esis as well as large-scale E. coli.
33. Luzhetskyy A, Mendez C, Salas JA, Bechthold A:Glycosyltransferases, important tools for drug design. CurrTop Med Chem 2008, 8:680-709.
34. Wohlgemuth R: Large-scale applications of hydrolasesin biocatalytic asymmetric synthesis. In Large-scaleAsymmetric Catalysis. Edited by Blaser HU, Federsel HJ.Weinheim: Wiley-VCH; 2010.
35. Gross RA, Ganesh M, Lu W: Enzyme-catalysis breathes new lifeinto polyester condensation polymerizations. TrendsBiotechnol 2010, 28:435-443.
36. Blasco MA, Thumann S, Wittmann J, Giannis: A, Groger H:Enantioselective biocatalytic synthesis of (S)-monastrol.Bioorg Med Chem Lett 2010, 20:4679-4682.
37.�
Fukuta Y, Komeda H, Yoshida Y, Asano Y: High yield synthesis of12-aminolauric acid by ‘enzymatic transcrystallization’ of v-laurolactam using v-laurolactam hydrolase from Acidivoraxsp. T31. Biosci Biotechnol Biochem 2009, 73:980-986.
An interesting high-yield enzymatic hydrolysis of v-laurolactam by v-laurolactam hydrolase from Acidivorax sp. has been developed. Crystal-line v-laurolactam, added to the enzyme solution, has been converted tocrystalline 12-aminolauric acid with the high volume yield of >200 g/l,high purity and >97% conversion.
38. Benz P, Muntwyler R, Wohlgemuth R: Chemoenzymaticsynthesis of chiral carboxylic acids via nitriles. J Chem TechnolBiotechnol 2007, 82:1087-1098.
39. Purkarthofer T, Skranc W, Schuster C, Griengl H: Potential andcapabilities of hydroxynitrile lyases as biocatalysts in thechemical industry. Appl Microbiol Biotechnol 2007, 76:309-320.
40. Andexer JN, Langermann JV, Kragl U, Pohl M: How to overcomelimitations in biotechnological processes—examples fromhydroxynitrile lyase applications. Trends Biotechnol 2009,27:599-607.
41. Koch K, van den Berg RJF, Nieuwland PJ, Wijtmans R,Schoemaker HE, van Hest JCM, Rutjes FPJT: Enzymaticenantioselective C–C-bond formation in microreactors.Biotechnol Bioeng 2008, 99:1028-1033.
42. Clapes P, Fessner WD, Sprenger GA, Samland AK: Recentprogress in stereoselective synthesis with aldolases. Curr OpinChem Biol 2010, 14:154-167.
43.��
Wolberg M, Dassen BHN, Schurmann M, Jennewein S,Wubbolts MG, Schoemaker HE, Mink D: Large-scale synthesisof new pyranoid building blocks based on aldolase-catalysedcarbon–carbon bond formation. Adv Synth Catal 2008,350:1751-1759.
Large-scale aldolase-catalyzed carbon–carbon bond formation, basedon a reaction discovered by CH Wong and coworkers, has permitted thehighly stereoselective synthesis of substituted d-lactones.
44. Muller M, Gocke D, Pohl M: Thiamin diphosphate in biologicalchemistry: exploitation of diverse thiamin diphosphate-dependent enzymes for asymmetric chemoenzymaticsynthesis. FEBS J 2009, 276:2894-2904.
45. Dominguez e Maria P, Stillger T, Pohl M, Kiesel M, Liese A,Groger H, Trauthwein H: Enantioselective C–C bond ligationusing recombinant Escherichia coli-whole-cell biocatalysts.Adv Synth Catal 2008, 350:165-173.
47. Shaeri J, Wright I, Rathbone EB, Wohlgemuth R, Woodley JM:Characterization of enzymatic D-xylulose 5-phosphatesynthesis. Biotechnol Bioeng 2008, 101:761-767.
48. Wohlgemuth R, Smith MEB, Dalby PA, Woodley JM:Transketolases. In Encyclopedia of Industrial Biotechnology.Edited by Flickinger MC. Hoboken, NJ: Wiley; 2010.
49.��
Stecher H, Tengg M, Ueberbacher BJ, Remler P, Schwab H,Griengl H, Gruber-Khadjawi M: Biocatalytic Friedel–Craftsalkylation using non-natural cofactors. Angew Chem Int Ed2009, 48:9546-9548.
The SAM-dependent methyltransferases NovO from Streptomyces spher-oides and CouO from Streptomyces rishiriensis, cloned and expressed inE. coli, have been shown to accept modified cofactors and to catalyze thesynthesis of a range of monosubstituted methylated, allylated, propargy-lated and benzylated arenes with excellent regioselectivity.
50.��
Lehwald P, Richter M, Rohr C, Liu HW, Muller M: Enantioselectiveintermolecular aldehyde–ketone cross-coupling through anenzymatic carboligation reaction. Angew Chem Int Ed 2010,49:1-5.
The thiamindiphosphate-dependent enzyme YerE has been shown tocatalyze the asymmetric cross-coupling of aldehydes and ketones tochiral teriary alcohols.
51.��
Seisser B, Zinkl R, Gruber K, Kaufmann F, Hafner A, Kroutil W:Cutting long syntheses short: access to non-natural tyrosinederivatives employing an engineered tyrosine phenol lyase.Adv Synth Catal 2010, 352:731-736.
The laborious and time-consuming multi-step synthesis of 3-substitutedtyrosine derivatives has been replaced by a single biocatalytic one-stepreaction using an engineered tyrosine phenol lyase.
52. Ma SM, Gruber J, Davis C, Newman L, Gray D, Wang A, Grate J,Huisman GW, Sheldon RA: A green-by-design biocatalyticprocess for atorvastatin intermediate. Green Chem 2010,12:81-86.
53. Kurlemann N, Lara M, Pohl M, Kroutil W, Liese A: Asymmetricsynthesis of chiral 2-hydroxy ketones by coupled biocatalyticalkene oxidation and C–C bond formation. J Mol Catal B:Enzymatic 2009, 61:111-116.
54. Leonard E, Runguphan W, O’Connor S, Jones Prather K:Opportunities in metabolic engineering to facilitate scalablealkaloid production. Nat Chem Biol 2009, 5:292-300.
55. Jani P, Emmert J, Wohlgemuth R: Process analysis ofmacrotetrolide biosynthesis during fermentation by means ofdirect infusion LC–MS. Biotechnol J 2008, 3:1-7.
56. Li K, He T, Li C, Feng XW, Wang N, Yu XQ: Lipase-catalyzeddirect Mannich reaction in water: utilization of biocatalyticpromiscuity for C–C bond formation in a ‘one-pot’ synthesis.Green Chem 2009, 11:777-779.
57.��
Znabet A, Ruijter E, Decanter FJJ, Kohler V, Helliwell M, Turner NJ,Orru RVA: Highly stereoselective synthesis of substitutedprolyl peptides using a combination of biocatalyticdesymmetrization and multicomponent reactions. AngewChem Int Ed 2010, 49:5289-5292.
A highly diastereoselective Ugi-multicomponent reaction of opticallyactive 3,4-disubstituted 1-pyrrolines, obtained by monoamineoxidaseN-catalyzed desymmetrization of the corresponding meso-pyrrolidines,with isocyanides and carboxylic acids has been developed for thesynthesis of substituted prolylpeptides.
58. Pornrapee V, Ramstrom O: Dynamic asymmetricmulticomponent resolution: lipase-mediated amidation of adouble dynamic covalent system. J Am Chem Soc 2009,131:14419-14425.
59. Kumar A, Maurya RA: An efficient baker’s yeast catalyzedsynthesis of 3,4-dihydropyrimidin-2-(1H)-ones. TetrahedronLett 2007, 48:4569-4571.
60. Wohlgemuth R: Modular and scalable biocatalytic tools forpractical safety, health and environmental improvements inthe production of speciality chemicals. BiocatalBiotransformation 2007, 25:178-185.
Current Opinion in Biotechnology 2010, 21:713–724
724 Chemical biotechnology
61. Wohlgemuth R: Tools and ingredients for the biocatalyticsynthesis of metabolites. Biotechnol J 2009, 9:1253-1265.
62. Tao J, Xu JH: Biocatalysis in development of greenpharmaceutical processes. Curr Opin Chem Biol 2009, 13:43-50.
63. Wohlgemuth R: Green production of fine chemicals by isolatedenzymes. In Biocatalysis for Green Chemistry and ChemicalProcess Development. Edited by Tao JA, Kazlauskas RJ.Hoboken, NJ: Wiley; 2010.
64. Walsh CT, Fischbach MA: Natural products version 2.0:connecting genes to molecules. J Am Chem Soc 2010,132:2469-2493.
65.��
Reetz MT: Directed evolution of enantioselective enzymes: anunconventional approach to asymmetric catalysis in organicchemistry. J Org Chem 2009, 74:5767-5778.
An excellent perspective on the principles, strategies and methods of thedirected evolution of enantioselective enzymes and their successes andfuture challenges in their applications as asymmetric catalysts in organicchemistry.
Rao D, Best D, Yoshihara A, Gullapalli P, Morimoto K,Woemaid MR, Wilson FX, Izumori K, Fleet GWJ: A conciseapproach to the synthesis of all twelve 5-deoxyhexoses:D-tagatose-3-epimerase — a reagent that is both specific andgeneral. Tetrahedron Lett 2009, 50:3559-3563.
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An interesting equilibration of 5-deoxy-D-fructose to 5-deoxy-D-psicoseand of 5-deoxy-L-psicose to 5-deoxy-L-fructose, providing substrates forthe preparation of all D-5-deoxy-aldohexoses and L-5-deoxy-aldo-hexoses.
68. Leutbecher H, Hajdok S, Braunberger C, Neumann M, Mika S,Conrad J, Beifuss U: Combined action of enzymes: the firstdomino reaction catalyzed by Agaricus bisporus. Green Chem2009, 11:676-679.
71. Yoshida T, Inami Y, Matsui T, Nagasawa T: Regioselectivecarboxylation of catechol by 3,4-dihydroxybenzoatedecarboxylase of Enterobacter cloacae P. Biotechnol Lett 2010,32:701-705.
72. Kirimura K, Gunji H, Wakayama R, Hattori T, Ishii Y: EnzymaticKolbe–Schmitt reaction to form salicylic acid from phenol:enzymatic characterization and gene identification of a novelenzyme, trichosporon moniliiforme salicylic aciddecarboxylase. Biochem Biophys Res Commun 2010, 394:279-284.