1932

Abstract

This review describes the status of the fields of biocatalysts and enzymes, as well as existing drawbacks, and recent advances in the areas deemed to represent drawbacks. Although biocatalysts are often highly active and extremely selective, there are still drawbacks associated with biocatalysis as a generally applicable technique: the lack of designability of biocatalysts; their limits of stability; and the insufficient number of well-characterized, ready-to-use biocatalysts.

There has been significant progress on the following fronts: () novel protein engineering tools, both experimental and computational, have significantly enhanced the toolbox for biocatalyst development. () The deactivation of biocatalysts under various stresses can be described quantitatively via rational models. There are several cases of spectacular leaps of stabilization after accumulating all stabilizing mutations found in earlier rounds. The concept that stabilization against one type of stress commonly also stabilizes against other types of stress is now experimentally considerably better founded than a few years ago. () A host of developments of novel biocatalysts in the past few years, in part fueled by improved designability and improved methods of stabilization, has considerably broadened the toolbox for synthetic chemistry.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-chembioeng-061114-123415
2015-07-24
2024-12-12
Loading full text...

Full text loading...

/deliver/fulltext/chembioeng/6/1/annurev-chembioeng-061114-123415.html?itemId=/content/journals/10.1146/annurev-chembioeng-061114-123415&mimeType=html&fmt=ahah

Literature Cited

  1. Turner NJ. 1.  2009. Directed evolution drives the next generation of biocatalysts. Nat. Chem. Biol. 5:568–74 [Google Scholar]
  2. Bornscheuer UT, Huisman GW, Kazlauskas RJ, Lutz S, Moore JC, Robins K. 2.  2012. Engineering the third wave of biocatalysis. Nature 485:185–94 [Google Scholar]
  3. Reetz MT. 3.  2013. Biocatalysis in organic chemistry and biotechnology: past, present, and future. J. Am. Chem. Soc. 135:12480–96 [Google Scholar]
  4. Chambers I, Frampton J, Goldfarb P, Affara N, McBain W, Harrison PR. 4.  1986. The structure of the mouse glutathione-peroxidase gene: the selenocysteine in the active-site is encoded by the ‘termination’ codon, TGA. EMBO J. 5:1221–27 [Google Scholar]
  5. Zinoni F, Birkmann A, Stadtman TC, Bock A. 5.  1986. Nucleotide-sequence and expression of the selenocysteine-containing polypeptide of formate dehydrogenase (formate-hydrogen-lyase-linked) from Escherichia coli. Proc. Natl. Acad. Sci. USA 83:4650–54 [Google Scholar]
  6. Srinivasan G, James CM, Krzycki JA. 6.  2002. Pyrrolysine encoded by UAG in Archaea: charging of a UAG-decoding specialized tRNA. Science 296:1459–62 [Google Scholar]
  7. Hao B, Gong WM, Ferguson TK, James CM, Krzycki JA, Chan MK. 7.  2002. A new UAG-encoded residue in the structure of a methanogen methyltransferase. Science 296:1462–66 [Google Scholar]
  8. Ngo JT, Tirrell DA. 8.  2011. Noncanonical amino acids in the interrogation of cellular protein synthesis. Acc. Chem. Res. 44:677–85 [Google Scholar]
  9. Xiao H, Chatterjee A, Choi SH, Bajjuri KM, Sinha SC, Schultz PG. 9.  2013. Genetic incorporation of multiple unnatural amino acids into proteins in mammalian cells. Angew. Chem. Int. Ed. 52:14080–83 [Google Scholar]
  10. Rosenzweig R, Kay LE. 10.  2014. Bringing dynamic molecular machines into focus by methyl-TROSY NMR. Annu. Rev. Biochem 83:291–15 [Google Scholar]
  11. Oikawa H, Kobayashi T, Katayama K, Suzuki Y, Ichihara A. 11.  1998. Total synthesis of (−)-solanapyrone A via enzymatic Diels-Alder reaction of prosolanapyrone. J. Organ. Chem. 63:8748–56 [Google Scholar]
  12. Reetz MT, Mondiere R, Carballeira JD. 12.  2007. Enzyme promiscuity: first protein-catalyzed Morita-Baylis-Hillman reaction. Tetrahedron Lett. 48:1679–81 [Google Scholar]
  13. Rothlisberger D, Khersonsky O, Wollacott AM, Jiang L, DeChancie J. 13.  et al. 2008. Kemp elimination catalysts by computational enzyme design. Nature 453:190–95 [Google Scholar]
  14. Abrahamson MJ, Vazquez-Figueroa E, Woodall NB, Moore JC, Bommarius AS. 14.  2012. Development of an amine dehydrogenase for synthesis of chiral amines. Angew. Chem. Int. Ed. 51:3969–72 [Google Scholar]
  15. Coelho PS, Brustad EM, Kannan A, Arnold FH. 15.  2013. Olefin cyclopropanation via carbene transfer catalyzed by engineered cytochrome P450 enzymes. Science 339:307–10 [Google Scholar]
  16. Fersht A. 16.  1999. Structure and Mechanism in Protein Science New York: Freeman [Google Scholar]
  17. Radzicka A, Wolfenden R. 17.  1995. A proficient enzyme. Science 267:90–93 [Google Scholar]
  18. Taylor EA, Palmer DRJ, Gerlt JA. 18.  2001. The lesser “burden borne” by o-succinylbenzoate synthase: an “easy” reaction involving a carboxylate carbon acid. J. Am. Chem. Soc. 123:5824–25 [Google Scholar]
  19. Wolfenden R, Snider MJ. 19.  2001. The depth of chemical time and the power of enzymes as catalysts. Acc. Chem. Res. 34:938–45 [Google Scholar]
  20. Notomista E, Cafaro V, Bozza G, Di Donato A. 20.  2009. Molecular determinants of the regioselectivity of toluene/o-xylene monooxygenase from Pseudomonas sp. strain OX1. Appl. Environ. Microbiol. 75:823–36 [Google Scholar]
  21. He ZQ, Nadeau LJ, Spain JC. 21.  2000. Characterization of hydroxylaminobenzene mutase from pNBZ139 cloned from Pseudomonas pseudoalcaligenes JS45. Eur. J. Biochem. 267:1110–16 [Google Scholar]
  22. Hu S, Huang J, Mei LH, Yu Q, Yao SJ, Jin ZH. 22.  2010. Altering the regioselectivity of cytochrome P450 BM-3 by saturation mutagenesis for the biosynthesis of indirubin. J. Mol. Catal. B: Enzymatic 67:29–35 [Google Scholar]
  23. Chenault HK, Dahmer J, Whitesides GM. 23.  1989. Kinetic resolution of unnatural and rarely occurring amino acids: enantioselective hydrolysis of N-acyl amino acids catalyzed by acylase I. J. Am. Chem. Soc. 111:6354–64 [Google Scholar]
  24. Wu Q, Soni P, Reetz MT. 24.  2013. Laboratory evolution of enantiocomplementary Candida antarctica lipase B mutants with broad substrate scope. J. Am. Chem. Soc. 135:1872–81 [Google Scholar]
  25. Reetz MT, Wang LW, Bocola M. 25.  2006. Directed evolution of enantioselective enzymes: iterative cycles of CASTing for probing protein-sequence space. Angew. Chem. Int. Ed. 45:1236–41 [Google Scholar]
  26. Bommarius AS, Drauz K, Hummel W, Kula MR, Wandrey C. 26.  1994. Some new developments in reductive amination with cofactor regeneration. Biocatalysis 10:37–47 [Google Scholar]
  27. Abrahamson MJ, Wong JW, Bommarius AS. 27.  2013. The evolution of an amine dehydrogenase biocatalyst for the asymmetric production of chiral amines. Adv. Synth. Catal. 355:1780–86 [Google Scholar]
  28. Reetz MT, Kahakeaw D, Lohmer R. 28.  2008. Addressing the numbers problem in directed evolution. ChemBioChem 9:1797–804 [Google Scholar]
  29. Reetz MT, Bocola M, Carballeira JD, Zha DX, Vogel A. 29a.  2005. Expanding the range of substrate acceptance of enzymes: combinatorial active-site saturation test. Angew. Chem. Int. Ed. 44:4192–96 [Google Scholar]
  30. Reetz MT. 29b.  2011. Laboratory evolution of stereoselective enzymes: a prolific source of catalysts for asymmetric reactions. Angew. Chem. Int. Ed. 50:138–74 [Google Scholar]
  31. Reetz MT, Carballeira JD. 30.  2007. Iterative saturation mutagenesis (ISM) for rapid directed evolution of functional enzymes. Nat. Protoc. 2:891–903 [Google Scholar]
  32. Bommarius AS, Schwarm M, Drauz K. 31.  2001. Comparison of different chemoenzymatic process routes to enantiomerically pure amino acids. Chimia 55:50–59 [Google Scholar]
  33. Rozzell JD. 32.  1999. Biocatalysis at commercial scale: myths and realities. Chim. Oggi-Chem. Today 17:42–47 [Google Scholar]
  34. Wandrey A, Seelbach K, Wandrey C. 33.  2006. Industrial Biotransformations Weinheim, Ger.: Wiley-VCH.570 [Google Scholar]
  35. Lumry R, Eyring H. 34.  1954. Conformation changes of proteins. J. Phys. Chem. 58:110–20 [Google Scholar]
  36. Rogers TA, Bommarius AS. 35.  2010. Utilizing simple biochemical measurements to predict lifetime output of biocatalysts in continuous isothermal processes. Chem. Eng. Sci. 65:2118–24 [Google Scholar]
  37. Eisenthal R, Danson MJ, Hough DW. 36.  2007. Catalytic efficiency and kcat/KM: a useful comparator?. Trends Biotechnol. 25:247–49 [Google Scholar]
  38. Ceccarelli EA, Carrillo N, Roveri OA. 37.  2008. Efficiency function for comparing catalytic competence. Trends Biotechnol. 26:117–18 [Google Scholar]
  39. Fox RJ, Clay MD. 38.  2009. Catalytic effectiveness, a measure of enzyme proficiency for industrial applications. Trends Biotechnol. 27:137–40 [Google Scholar]
  40. Palackal N, Brennan Y, Callen WN, Dupree P, Frey G. 39.  et al. 2004. An evolutionary route to xylanase process fitness. Protein Sci. 13:494–503 [Google Scholar]
  41. Voigt CA, Martinez C, Wang Z-G, Mayo SL, Arnold FH. 40.  2002. Protein building blocks preserved by recombination, Nature Struct. Biol 9:553–58 [Google Scholar]
  42. Meyer MM, Silberg JJ, Voigt CA, Endelman JB, Mayo SL. 41.  et al. 2003. Library analysis of SCHEMA-guided protein recombination. Protein Sci. 12:1686–93 [Google Scholar]
  43. Heinzelman P, Snow CD, Wu I, Nguyen C, Villalobos A. 42.  et al. 2009. A family of thermostable fungal cellulases created by structure-guided recombination. Proc. Natl. Acad. Sci. USA 106:5610–15 [Google Scholar]
  44. Heinzelman P, Snow CD, Smith MA, Yu XL, Kannan A. 43.  et al. 2009. SCHEMA recombination of a fungal cellulase uncovers a single mutation that contributes markedly to stability. J. Biol. Chem. 284:26229–33 [Google Scholar]
  45. Heinzelman P, Komor R, Kanaan A, Romero P, Yu XL. 44.  et al. 2010. Efficient screening of fungal cellobiohydrolase class I enzymes for thermostabilizing sequence blocks by SCHEMA structure-guided recombination. Protein Eng. Des. Select. 23:871–80 [Google Scholar]
  46. Anbar M, Bayer EA. 45.  2012. Approaches for improving thermostability characteristics in cellulases. Cellulases 510:261–71 [Google Scholar]
  47. Steipe B, Schiller B, Pluckthun A, Steinbacher S. 46.  1994. Sequence statistics reliably predict stabilizing mutations in a protein domain. J. Mol. Biol. 240:188–92 [Google Scholar]
  48. Lehmann M, Pasamontes L, Lassen SF, Wyss M. 47.  2000. The consensus concept for thermostability engineering of proteins. Biochim. Biophys. Acta-Protein Struct. Mol. Enzymol.1543408–15 [Google Scholar]
  49. Lehmann M, Loch C, Middendorf A, Studer D, Lassen SF. 48.  et al. 2002. The consensus concept for thermostability engineering of proteins: further proof of concept. Protein Eng. 15:403–11 [Google Scholar]
  50. Amin N, Liu AD, Ramer S, Aehle W, Meijer D. 49.  et al. 2004. Construction of stabilized proteins by combinatorial consensus mutagenesis. Protein Eng. Des. Sel. 17:787–93 [Google Scholar]
  51. Vazquez-Figueroa E, Yeh V, Broering JM, Chaparro-Riggers JF, Bommarius AS. 50.  2008. Thermostable variants constructed via the structure-guided consensus method also show increased stability in salts solutions and homogeneous aqueous-organic media. Protein Eng. Des. Sel. 21:673–80 [Google Scholar]
  52. Baik SH, Ide T, Yoshida H, Kagami O, Harayama S. 51.  2003. Significantly enhanced stability of glucose dehydrogenase by directed evolution. Appl. Microbiol. Biotechnol. 61:329–35 [Google Scholar]
  53. Reetz MT, Soni P, Acevedo JP, Sanchis J. 52.  2009. Creation of an amino acid network of structurally coupled residues in the directed evolution of a thermostable enzyme. Angew. Chem. Int. Ed. 48:8268–72 [Google Scholar]
  54. Blum JK, Ricketts MD, Bommarius AS. 53.  2012. Improved thermostability of AEH by combining B-FIT analysis and structure-guided consensus method. J. Biotechnol. 160:214–21 [Google Scholar]
  55. Wijma HJ, Floor RJ, Jekel PA, Baker D, Marrink SJ, Janssen DB. 54.  2014. Computationally designed libraries for rapid enzyme stabilization. Protein Eng. Des. Sel. 27:49–58 [Google Scholar]
  56. Bommarius AS, Paye MF. 55.  2013. Stabilizing biocatalysts. Chem. Soc. Rev. 42:6534–65 [Google Scholar]
  57. Cowan DA. 56.  1997. Thermophilic proteins: stability and function in aqueous and organic solvents. Comp. Biochem. Physiol.-Mol. Integr. Physiol. 118:429–38 [Google Scholar]
  58. Owusu RK, Cowan DA. 57.  1989. Correlation between microbial protein thermostability and resistance to denaturation in aqueous-organic solvent 2-phase systems. Enzyme Microb. Technol. 11:568–74 [Google Scholar]
  59. Hao JJ, Berry A. 58.  2004. A thermostable variant of fructose bisphosphate aldolase constructed by directed evolution also shows increased stability in organic solvents. Protein Eng. Des. Sel. 17:689–97 [Google Scholar]
  60. Reetz MT, Soni P, Fernandez L, Gumulya Y, Carballeira JD. 59.  2010. Increasing the stability of an enzyme toward hostile organic solvents by directed evolution based on iterative saturation mutagenesis using the B-FIT method. Chem. Commun. 46:8657–58 [Google Scholar]
  61. Adalbjörnsson BV, Toogood HS, Fryszkowska A, Pudney CR, Jowitt TA. 60.  et al. 2010. Biocatalysis with thermostable enzymes: structure and properties of a thermophilic ‘ene’-reductase related to old yellow enzyme. ChemBioChem 11:197–207 [Google Scholar]
  62. Sharma S, Mittal A, Gupta VK, Singh H. 61.  2007. Improved stabilization of microencapsulated Cathepsin B in harsh conditions. Enzyme Microb. Technol. 40:337–42 [Google Scholar]
  63. Slusarczyk H, Felber S, Kula MR, Pohl M. 62.  2000. Stabilization of NAD-dependent formate dehydrogenase from Candida boidinii by site-directed mutagenesis of cysteine residues. Eur. J. Biochem. 267:1280–89 [Google Scholar]
  64. Bommarius AS, Karau A. 63.  2005. Deactivation of formate dehydrogenase (FDH) in solution and at gas-liquid interfaces. Biotechnol. Prog. 21:1663–72 [Google Scholar]
  65. Gadler P, Reiter TC, Hoelsch K, Weuster-Botz D, Faber K. 64.  2009. Enantiocomplementary inverting sec-alkylsulfatase activity in cyano- and thio-bacteria Synechococcus and Paracoccus spp.: selectivity enhancement by medium engineering. Tetrahedron-Asymmetry 20:115–18 [Google Scholar]
  66. Schober M, Gadler P, Knaus T, Kayer H, Birner-Grunberger R. 65.  et al. 2011. A stereoselective inverting sec-alkylsulfatase for the deracemization of sec-alcohols. Org. Lett. 13:4296–99 [Google Scholar]
  67. Schober M, Knaus T, Toesch M, Macheroux P, Wagner U, Faber K. 66.  2012. The substrate spectrum of the inverting sec-alkylsulfatase Pisa1. Adv. Synth. Catal. 354:1737–42 [Google Scholar]
  68. Schober M, Toesch M, Knaus T, Strohmeier GA, van Loo B. 67.  et al. 2013. One-pot deracemization of sec-alcohols: enantioconvergent enzymatic hydrolysis of alkyl sulfates using stereocomplementary sulfatases. Angew. Chem. Int. Ed. 52:3277–79 [Google Scholar]
  69. Lara M, Mutti FG, Glueck SM, Kroutil W. 68.  2008. Biocatalytic cleavage of alkenes with O2 and Trametes hirsuta G FCC 047. Eur. J. Organ. Chem. 2008:213668–72 [Google Scholar]
  70. Rajagopalan A, Mutti FG, Kroutil W. 69.  2012. Biocatalytic cleavage of alkenes with oxygen and Trametes hirsuta G FCC047. Practical Methods for Biocatalysis and Biotransformations 2 J. Whittall, P. Sutton 199–202 West Sussex, UK: Wiley388 [Google Scholar]
  71. Lara M, Mutti FG, Glueck SM, Kroutil W. 70.  2009. Oxidative enzymatic alkene cleavage: indications for a nonclassical enzyme mechanism. J. Am. Chem. Soc. 131:5368–69 [Google Scholar]
  72. Rajagopalan A, Schober M, Emmerstorfer A, Hammerer L, Migglautsch A. 71.  et al. 2013. Enzymatic aerobic alkene cleavage catalyzed by a Mn3+-dependent proteinase A homologue. ChemBioChem 14:2427–30 [Google Scholar]
  73. Wallner S, Winkler A, Riedl S, Dully C, Horvath S. 72.  et al. 2012. Catalytic and structural role of a conserved active site histidine in berberine bridge enzyme. Biochemistry 51:6139–47 [Google Scholar]
  74. Schrittwieser JH, Resch V, Sattler JH, Lienhart WD, Durchschein K. 73.  et al. 2011. Biocatalytic enantioselective oxidative C-C coupling by aerobic C-H activation. Angew. Chem. Int. Ed. 50:1068–71 [Google Scholar]
  75. Resch V, Schrittwieser JH, Wallner S, Macheroux P, Kroutil W. 74.  2011. Biocatalytic oxidative C-C bond formation catalysed by the berberine bridge enzyme: optimal reaction conditions. Adv. Synth. Catal. 353:2377–83 [Google Scholar]
  76. Schrittwieser JH, Groenendaal B, Resch V, Ghislieri D, Wallner S. 75.  et al. 2014. Deracemization by simultaneous bio-oxidative kinetic resolution and stereoinversion. Angew. Chem. Int. Ed. 53:3731–34 [Google Scholar]
  77. Ghislieri D, Green AP, Pontini M, Willies SC, Rowles I. 76.  et al. 2013. Engineering an enantioselective amine oxidase for the synthesis of pharmaceutical building blocks and alkaloid natural products. J. Am. Chem. Soc. 135:10863–69 [Google Scholar]
  78. Atkin KE, Reiss R, Koehler V, Bailey KR, Hart S. 77.  et al. 2008. The structure of monoamine oxidase from Aspergillus niger provides a molecular context for improvements in activity obtained by directed evolution. J. Mol. Biol. 384:1218–31 [Google Scholar]
  79. Eve TSC, Wells A, Turner NJ. 78.  2007. Enantioselective oxidation of O-methyl-N-hydroxylamines using monoamine oxidase N as catalyst. Chem. Commun. 2007:151530–31 [Google Scholar]
  80. Kohler V, Bailey KR, Znabet A, Raftery J, Helliwell M, Turner NJ. 79.  2010. Enantioselective biocatalytic oxidative desymmetrization of substituted pyrrolidines. Angew. Chem. Int. Ed. 49:2182–84 [Google Scholar]
  81. Znabet A, Polak MM, Janssen E, de Kanter FJJ, Turner NJ. 80.  et al. 2010. A highly efficient synthesis of telaprevir by strategic use of biocatalysis and multicomponent reactions. Chem. Commun. 46:7918–20 [Google Scholar]
  82. O'Reilly E, Iglesias C, Ghislieri D, Hopwood J, Galman JL. 81.  et al. 2014. A regio-and stereoselective w-transaminase/monoamine oxidase cascade for the synthesis of chiral 2,5-disubstituted pyrrolidines. Angew. Chem. Int. Ed. 53:2447–50 [Google Scholar]
  83. Constable DJC, Dunn PJ, Hayler JD, Humphrey GR, Leazer JL. 82.  et al. 2007. Key green chemistry research areas—a perspective from pharmaceutical manufacturers. Green Chem. 9:411–20 [Google Scholar]
  84. Brunhuber NMW, Thoden JB, Blanchard JS, Vanhooke JL. 83.  2000. Rhodococcus L-phenylalanine dehydrogenase: kinetics, mechanism, and structural basis for catalytic specificity. Biochemistry 39:9174–87 [Google Scholar]
  85. Ringenberg MR, Ward TR. 84.  2011. Merging the best of two worlds: artificial metalloenzymes for enantioselective catalysis. Chem. Commun. 47:8470–76 [Google Scholar]
  86. Lo C, Ringenberg MR, Gnandt D, Wilson Y, Ward TR. 85.  2011. Artificial metalloenzymes for olefin metathesis based on the biotin-(strept)avidin technology. Chem. Commun. 47:12065–67 [Google Scholar]
  87. Durrenberger M, Ward TR. 86.  2014. Recent achievements in the design and engineering of artificial metalloenzymes. Curr. Opin. Chem. Biol. 19:99–106 [Google Scholar]
  88. Mclntosh JA, Farwell CC, Arnold FH. 87.  2014. Expanding P450 catalytic reaction space through evolution and engineering. Curr. Opin. Chem. Biol. 19:126–34 [Google Scholar]
  89. McIntosh JA, Coelho PS, Farwell CC, Wang ZJ, Lewis JC. 88.  et al. 2013. Enantioselective intramolecular C-H amination catalyzed by engineered cytochrome P450 enzymes in vitro and in vivo. Angew. Chem. Int. Ed. 52:9309–12 [Google Scholar]
  90. Wang ZJ, Peck NE, Renata H, Arnold FH. 89.  2014. Cytochrome P450-catalyzed insertion of carbenoids into N-H bonds. Chem. Sci. 5:598–601 [Google Scholar]
  91. Dodani SC, Cahn JKB, Heinisch T, Brinkmann-Chen S, McIntosh JA, Arnold FH. 90.  2014. Structural, functional, and spectroscopic characterization of the substrate scope of the novel nitrating cytochrome P450 TxtE. Chembiochem 15:2259–67 [Google Scholar]
  92. Coelho PS, Wang ZJ, Ener ME, Baril SA, Kannan A. 91.  et al. 2013. A serine-substituted P450 catalyzes highly efficient carbene transfer to olefins in vivo. Nat. Chem. Biol. 9:485–87 [Google Scholar]
  93. Wang ZJ, Renata H, Peck NE, Farwell CC, Coelho PS, Arnold FH. 92.  2014. Improved cyclopropanation activity of histidine-ligated cytochrome P450 enables the enantioselective formal synthesis of levomilnacipran. Angew. Chem. Int. Ed. 53:6810–13 [Google Scholar]
  94. Khersonsky O, Rothlisberger D, Dym O, Albeck S, Jackson CJ. 93.  et al. 2010. Evolutionary optimization of computationally designed enzymes: Kemp eliminases of the KE07 series. J. Mol. Biol. 396:1025–42 [Google Scholar]
  95. Khersonsky O, Kiss G, Rothlisberger D, Dym O, Albeck S. 94.  et al. 2012. Bridging the gaps in design methodologies by evolutionary optimization of the stability and proficiency of designed Kemp eliminase KE59. Proc. Natl. Acad. Sci. USA 109:10358–63 [Google Scholar]
  96. Blomberg R, Kries H, Pinkas DM, Mittl PRE, Grutter MG. 95.  et al. 2013. Precision is essential for efficient catalysis in an evolved Kemp eliminase. Nature 503:418–21 [Google Scholar]
  97. Hohne M, Bornscheuer UT. 96.  2014. Protein engineering from “scratch” is maturing. Angew. Chem. Int. Ed. 53:1200–2 [Google Scholar]
  98. Patel JM. 97.  2009. Biocatalytic synthesis of atorvastatin intermediates. J. Mol. Catal. B: Enzym. 61:123–28 [Google Scholar]
  99. Muller M. 98.  2005. Chemoenzymatic synthesis of building blocks for statin side chains. Angew. Chem. Int. Ed. 44:362–65 [Google Scholar]
  100. Wolberg M, Hummel W, Wandrey C, Muller M. 99.  2000. Highly regio- and enantioselective reduction of 3,5-dioxocarboxylates. Angew. Chem. Int. Ed. 39:4306–8 [Google Scholar]
  101. Wolberg M, Villela M, Bode S, Geilenkirchen P, Feldmann R. 100.  et al. 2008. Chemoenzymatic synthesis of the chiral side-chain of statins: application of an alcohol dehydrogenase catalysed ketone reduction on a large scale. Bioprocess Biosyst. Eng. 31:183–91 [Google Scholar]
  102. Wolberg M, Hummel W, Muller M. 101.  2001. Biocatalytic reduction of β,δ-diketo esters: a highly stereoselective approach to all four stereoisomers of a chlorinated β,δ-dihydroxy hexanoate. Chem. Eur. J. 7:4562–71 [Google Scholar]
  103. Tao JH, Xu JH. 102.  2009. Biocatalysis in development of green pharmaceutical processes. Curr. Opin. Chem. Biol. 13:43–50 [Google Scholar]
  104. Fox RJ, Davis SC, Mundorff EC, Newman LM, Gavrilovic V. 103.  et al. 2007. Improving catalytic function by ProSAR-driven enzyme evolution. Nat. Biotechnol. 25:338–44 [Google Scholar]
  105. Martinez CA, Hu S, Dumond Y, Tao J, Kelleher P, Tully L. 104.  2008. Development of a chemoenzymatic manufacturing process for pregabalin. Organ. Process Res. Dev. 12:392–98 [Google Scholar]
  106. Winkler CK, Clay D, Davies S, O'Neill P, McDaid P. 105.  et al. 2013. Chemoenzymatic asymmetric synthesis of pregabalin precursors via asymmetric bioreduction of β-cyanoacrylate esters using ene-reductases. J. Organ. Chem. 78:1525–33 [Google Scholar]
  107. Winkler CK, Clay D, Turrini NG, Lechner H, Kroutil W. 106.  et al. 2014. Nitrile as activating group in the asymmetric bioreduction of β-cyanoacrylic acids catalyzed by ene-reductases. Adv. Synth. Catal. 356:1878–82 [Google Scholar]
  108. Hanson RL, Goldberg SL, Brzozowski DB, Tully TP, Cazzulino D. 107.  et al. 2007. Preparation of an amino acid intermediate for the dipeptidyl peptidase IV inhibitor, saxagliptin, using a modified phenylalanine dehydrogenase. Adv. Synth. Catal. 349:1369–78 [Google Scholar]
  109. Savile CK, Janey JM, Mundorff EC, Moore JC, Tam S. 108.  et al. 2010. Biocatalytic asymmetric synthesis of chiral amines from ketones applied to sitagliptin manufacture. Science 329:305–9 [Google Scholar]
  110. Hall M, Bommarius AS. 109.  2011. Enantioenriched compounds via enzyme-catalyzed redox reactions. Chem. Rev. 111:4088–110 [Google Scholar]
/content/journals/10.1146/annurev-chembioeng-061114-123415
Loading
/content/journals/10.1146/annurev-chembioeng-061114-123415
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error