Bioorganic & Medicinal Chemistry 22 (2014) 5604–5612

Contents lists available at ScienceDirect

Bioorganic & Medicinal Chemistry journal homepage: www.elsevier.com/locate/bmc

Recent advances in biocatalyst discovery, development and applications Guang Yang, Yousong Ding ⇑ Department of Medicinal Chemistry, University of Florida, Gainesville, FL 32610, USA

a r t i c l e

i n f o

Article history: Received 14 April 2014 Revised 13 June 2014 Accepted 17 June 2014 Available online 25 June 2014 Keywords: Biocatalyst Metagenomics Database mining Protein engineering Transaminases Cytochrome P450s Baeyer–Villiger monooxygenases

a b s t r a c t Enzymes catalyze a wide range of biotransformations and have a great potential as environmentally friendly alternatives to classical chemical catalysts in various industrial applications. Recently, advanced techniques and strategies in enzyme discovery and engineering have led to the significant expansion of the quantity and functional diversity of biocatalysts, which has further allowed broader uses of biocatalysts in new processes, especially those traditionally enabled only by chemical catalysts. Here we highlight some of these recent advances with the focus on new approaches in biocatalyst discovery and development, and discuss new applications of selected biocatalysts including transaminases, cytochrome P450s, and Baeyer–Villiger monooxygenases. Ó 2014 Elsevier Ltd. All rights reserved.

1. Introduction Enzymes carry out a wide array of chemical reactions essential for life and have increasingly been used as alternative catalysts in industrial processes such as the production of pharmaceuticals, agrochemicals, pesticides and insecticides.1 Compared with chemical catalysts, the use of biocatalysts offers a number of distinct advantages such as high efficiency, high degree of selectivity, mild reaction conditions, and environmental friendliness.2 These features have been driving enormous efforts in creating biocatalysts to fulfill consumer demands for new and higher quality products, industrial demand for improved efficiency, and society and government pressures for ‘greener’ technologies. The huge potential of biocatalysts can be realized only if we can discover and develop suitable enzymes for a given industrial application. In the last few years, new approaches have been developed to discover new enzymes and new homologs to suit industrial processes. Generally, enzymes evolved for biological systems rarely perform optimally under conditions favorable for chemical synthesis such as high concentration of organic solvents and extreme conditions of pH, temperature and/or pressure.3–5 However, the pool available for biocatalyst selection and development is primarily comprised of enzymes only from easily accessible and cultivable

⇑ Corresponding author. Tel.: +1 352 273 7742; fax: +1 352 392 9455. E-mail address: [email protected]fl.edu (Y. Ding). http://dx.doi.org/10.1016/j.bmc.2014.06.033 0968-0896/Ó 2014 Elsevier Ltd. All rights reserved.

organisms, while about 99% of the host organisms on Earth are uncultivable and remain unexplored for discovery of novel biocatalysts.6 Exploitation of this untouched resource will not only provide numerous unidentified enzymes from microorganisms residing in environmental conditions similar to those of industrial processes (pH, pressure, temperature, etc.), but also allow developing new processes.7,8 Indeed, the efficiency of this approach was well demonstrated ten years ago.9 In this study, >600 libraries were prepared with environmental DNAs of both cultivable and uncultivable microbes, and library screening led to the increase in number of total identified nitrilases by 7 times. Besides, exponential growth of new enzyme structures, enormous amount of -omics data, and rapid advances of bioinformatics tools together are revolutionizing our strategies in identifying and characterizing new enzymes from existing and new databases.10–12 Protein engineering technologies are often used to change and optimize enzyme traits for chemical reactions. Both rational design and directed evolution have been used to tailor enzyme properties.13,14 Rational design requires thorough understanding of parental structure, catalytic mechanism, interactions, and even dynamics in order to identify mutations that would lead to desired enzyme properties, especially the high level of performance required for industrial applications. Such information is often lacking, particularly when new enzymes are used in biocatalyst development. Evolutionary approach that only requires functional expression in a recombinant host and a high throughput screening or selection is commonly used to improve enzyme fitness. It mimics Darwinian

G. Yang, Y. Ding / Bioorg. Med. Chem. 22 (2014) 5604–5612

evolution process in laboratory settings and importantly on a significantly shorter time scale through iterative cycles of mutagenesis and accumulation of beneficial mutations.15,16 Freed from natural constraints, computational protein design is another promising approach in developing biocatalysts. Very recently, the Hilvert group improved the activities of computationally designed biocatalysts to the level of natural enzymes by combining rational design and directed evolution approaches.17–19 All of the above enabling techniques offer exciting new opportunities to develop biocatalysts for better and new applications. In this review, we discuss recent advances in the discovery of enzymes as biocatalysts and their developments with new approaches. Over the past few years, a number of applications with new biocatalysts have been reported. Given space limit, we discuss only a few in this review, and refer readers to two recent excellent reviews for gaining additional information.20,21 2. New approaches in the discovery of novel biocatalysts Historically, the discovery of enzymes is mostly based on the culture enrichment and screening of crude extracts from natural sources.22,23 These approaches have led to the identification and characterization of a large number of biocatalysts that have been used in many applications. However, the cultivable microorganisms represent only 4400 folds through random mutagenesis.18 Therefore, combination of all three types of protein engineering approaches is expected to expand the scope and breadth of discovery and development of biocatalysts for a given process. 4. Novel applications of biocatalysts Currently, hydrolases such as lipases and esterases are the most frequently used biocatalysts in industrial organic synthesis.94 Cofactor independence and a wide range of substrate promiscuity are two outstanding features making this class of enzymes attractive.95,96 In the recent years, a number of novel biocatalysts have been discovered, isolated and engineered to display fascinating catalytic properties, further expanding the range of biotransformations. In this section, we will highlight some examples of these new enzymes/applications. 4.1. Transaminases Transaminases are pyridoxal-50 -phosphate (PLP) dependent enzymes that catalyze asymmetric amine transfer reactions between an amine and a ketone. This critical biotransformation has been applied mainly in three ways: (1) kinetic resolution of racemic amines into an enantiomerically pure amine via enantioselective deamination with a theoretical yield of 650%, (2) asymmetric synthesis from prochiral ketones to produce enantiomerically pure amine products via reductive amination with a yield of 6100%, and (3) deracemization to convert a racemate into a single enantiomer with 100% theoretical yield.97 Transaminases can be grouped into two primary classes.98 The first class is named as a-transaminases that require a carboxylic acid group at a-position of their ketone and amine substrates and can be useful for the synthesis of non-natural amino acids. The second class is denoted as x-transaminases that broadly cover those transferring a terminal amino group to any position other than a carbon in the substrate. Given the ease to prepare (R)- or (S)-amines from ketones in one-step enzyme reactions and the importance of chiral amines in diverse products such as pharmaceuticals, x-transaminases have been extensively studied and used.99 Recent advances in transaminase studies are reflected in using both metagenomics-based approaches and database mining to identify desirable novel enzymes. For example, a novel b-transaminase (Kat) was discovered through sequence searching of the metagenome of anaerobic digester of a municipal wastewater treatment plant (Fig. 3A).100 This enzyme participated in an alternative lysine fermentation pathway by converting 3-aminobutyryl-CoA into acetoacetyl-CoA with the 2-ketoglutarate as amine acceptor. It strictly required the CoA moiety in its substrates but showed broad flexibility toward both aliphatic and aromatic substitutions on the substrates. In another study, the Bornscheuer group developed an in silico strategy to discover transaminases.12 His group first examined crystal structures of many transaminases deposited in Protein Data Bank to identify and predict important amino acid residues determining enzyme enantioselectivity and then mined proteins carrying these determinant residues from the databases. Using this strategy, 17 (R)-selective amine transaminases were discovered, and synthesized several (R)-amines with up to >99% enantiomeric excess (ee) (Fig. 3B).12 Protein engineering continuously created new opportunities to generate novel transaminases with tailored activities. For instance, researchers from Codexis and Merck have recently developed novel x-transaminases for the production of antidiabetic drug sitagliptin on industrial scale (Fig. 3C).101 This engineering study started with a (R)-selective x-transaminase which was only active towards a small substrate. The authors then performed 11 rounds

G. Yang, Y. Ding / Bioorg. Med. Chem. 22 (2014) 5604–5612

5609

Figure 3. Selected reactions catalyzed by newly discovered and engineered transaminases. Except A, all products carrying the amine group were labeled in red.

of protein engineering by combining modeling, saturation mutagenesis, gene shuffling and random mutagenesis to craft the improved biocatalysts. The final enzyme carrying 25 mutations robustly produced sitagliptin with 99.9% ee at a productivity of 25 g/L/h. Remarkably, this biocatalyst was tolerant to up to 275 g/L of substrate and 60% of DMSO.101 Isopropylamine (IPM) as amine donor was converted into easily removed acetone in the production process. In another study, a group of Pfizer scientists combined several protein engineering approaches, including modeling, docking, crystallization, ration design, saturation mutagenesis, consensus design, and DNA synthesis, to improve performances of a Vibrio fluvialis aminotransferase (Vfat) for the synthesis of (3S,5R)-ethyl 3-amino-5-methyloctanoate (Fig. 3D).102 The product is a key intermediate in the synthesis of imagabalin, an advanced drug candidate for the treatment of generalized anxiety disorder. In this study, only 60 times. 4.2. Cytochrome P450s In Nature, cytochrome P450s catalyze a wide array of reactions on a number of substrates, such as hydroxylation, epoxidation, sulfoxidation, aryl–aryl coupling, oxidative and reductive dehalogenation.103–105 Many of these reactions are important in chemical synthesis, and P450s have thus been extensively studied

and engineered in the past decades.16,106,107 Several excellent reviews already summarized applications of wild-type and engineered P450s in various reactions.16,103,105 Here, we cover only several latest applications. One of the most intriguing P450-promoted reactions is the direct nitration of tryptophan catalyzed by TxtE (Fig. 4A).108 The nitro group is an important, functional moiety of a broad range of fine chemicals such as drugs, pesticides, and explosives. Classic electrophilic nitration reaction relying on strong acids is one of the best studied chemical reactions and has been used by chemical industry to produce nitrated compounds for a long time.109 In Nature, over 200 nitrated natural products with a great degree of structural diversity have been isolated,110 and enzymatic Noxygenation is the predominant mechanism to produce the nitro group from a preinstalled amine group.111 TxtE is unique as the first enzyme enabling direct nitration with NO as co-substrate. Its reaction mechanism remains unclear, but may involve neither compound I nor iron-peroxo intermediate. This work along with many other examples illustrated the creativity of Nature in exploring the common protein space to deliver new chemistry, and further demonstrated the importance of new enzyme discovery. Very interestingly, a non-heme iron-dependent halogenase (SyrB2) was shown to catalyze aliphatic nitration and azidation with  112 anions NO The 2 and N3 as donors, respectively (Fig. 4B). anion–ferryl complex was believed to be the active intermediate and confirmed by spectral analysis. Furthermore, the authors

Figure 4. Novel reactions promoted by P450s (A, C and D) and a non-heme iron-dependent halogenase (B). All novel chemistry were labeled in red.

5610

G. Yang, Y. Ding / Bioorg. Med. Chem. 22 (2014) 5604–5612

Figure 5. Oxidative transformations of ketones by engineered BVMOs. All inserted oxygen atoms were labeled in red. Two substrates not accepted by wild type PAMO were labeled in blue.

rationally designed an A118G mutation to reduce native halogen anion binding by about 1000 times, thereby dedicating the enzyme specific to C–N coupling reactions. The efficiency of nitration and azidation were improved by 2.5-fold and 13-fold in corresponding mutant reactions. These examples suggest that continuous exploration of iron-based enzymes is likely to unveil more novel chemistry. Two other important findings about P450-promoted new chemistry were carbene and nitrene transfer reactions. Although iron porphyrins were known to transfer carbene from diazo precursors to olefins, leading to the formation of cyclopropanes, Coelho et al. very recently showed that P450BM3 variant enabled this reaction in an enantioselective manner (Fig. 4C).113,114 Engineering the variant at T268 and a universally conserved cysteine as the heme iron axial coordinator further improved activity, diastereoselectivity, and enantioselectivity of carbene transfer reactions.115 In a subsequent study, Wang et al. further demonstrated that a carbene N–H insertion reaction was catalyzed by an engineered P450BM3 variant, and the reaction proceeded in a strictly controlled manner and with high turnover numbers.116 The versatility of P450s was further showcased by its catalyzed intramolecular formation of C–N bonds using unnatural sulfonyl azides as substrates (Fig. 4D).117 This reaction presumably involved the transfer of nitrene from its azide precursors. Interestingly, the same mutation of conserved cysteine into the serine that previously benefited the carbene transfer, if not necessary, also improved enzyme behaviors in C–H amination reactions. However, the Fasan group in a parallel study found that P450BM3 variants retaining the native cysteine residue supported the similar intramolecular nitrene transfer reaction.118 The variants identified in this work showed equal or even higher efficiency, high total turnovers, excellent regioselectivity, and considerable stereoselectivity. These studies pointed out the conservation and diversity of the protein sequence space in promoting similar reactions. Considering the recent development and increasing needs from synthetic biology, the ability of P450s to assume new catalytic functions in natural and artificial contexts will certainly be valuable for many aspects of industrial applications.

asymmetric synthesis in the past decade, which were already reviewed in two recent papers.120,121 Here we briefly highlight new advances in the discovery, development and applications of this type of enzymes. Similar to many other types of biocatalysts, BVMO studies have been rapidly advanced in the discovery of new enzymes. For instance, Singh et al. isolated a BMVO from an effluent treatment plant metagenomic library,122 while the Grogan group applied the genome mining approach to discover 23 putative BVMO genes from Rhodococcus jostii genome.123 Subsequent heterologous expression of all identified genes yielded 13 soluble proteins, all of which exhibited activities toward at least one of seven selected substrates. Another recent study identified 116 new BVMO sequences from the Universal Protein Resource database by searching sequence homology of type I BVMO proteins, and evaluated functional importance of conserved residues in enzyme catalysis and substrate specificity.124 The enormous diversity of catalytic properties of BVMOs allowed enzyme applications in the production of many different classes of valuable chemicals. However, the narrow substrate scope of wild-type enzymes and low thermostability often limit their usage in catalyzing reactions on chemicals very dissimilar to native substrates.125 Protein engineering has been undertaken to optimize enzyme performances.120 For example, Fraaije and coworkers created three chimeric BVMOs through structure-guided subdomain exchanges.126 The C-terminal domain of a thermostable PAMO was replaced with respective subdomains of three other BVMOs with low sequence identities. Resultant chimeric enzymes retained original thermostability, and one even exhibited new substrate preference toward progesterone (Fig. 5A). In another study, both apparent Tm and half-life of one labile BVMO were significantly improved by rationally incorporating one disulfide bond through in silico design .127 In the last a few years, several groups have actively expanded BVMO substrate scopes using protein engineering approaches. For example, the Reetz group recently used the ISM approach to simultaneously mutate multiple sites of a thermostable PAMO.80 The best-evolved mutants exhibited >99% diastereoselectivity toward three substrates including two not accepted by the wild type enzyme (Fig. 5B).

4.3. Baeyer–Villiger monooxygenases 5. Conclusion Baeyer–Villiger monooxygenases (BVMOs) are flavin-containing monooxygenases that oxidatively desymmetrize prochiral ketones or kinetic resolution of racemic substrates with the formation of esters or lactones.119 Compared with their chemical counterparts, enzyme catalysis eliminates the use of potentially harmful reagents (i.e., green chemistry) and provides significantly improved enantio- and regio-selectivity. Therefore, BVMOs including cyclohexanone monooxygenase (CHMO) from Acinetobacter calcoaceticus NCIMB 9871 and phenylacetone monooxygenase (PAMO) from Thermobifida fusca have been extensively investigated for

Enzymes are increasingly being used in various industrial applications as an environmentally friendly alternative to chemical catalysts. For a long time the discovery of new enzymes was based on classic cultivation-dependent methods mainly accounting for less than 1% of all available microbes. Recent breakthroughs in many fields such as molecular biology, bioinformatics and protein engineering have revolutionized approaches for the discovery and development of biocatalysts. For example, metagenomics-based approaches and database mining have already succeeded in

G. Yang, Y. Ding / Bioorg. Med. Chem. 22 (2014) 5604–5612

discovering new enzymes for biotechnological processes and provided a new basis to study novel protein structures and catalytic mechanisms. In this context, improved screening and detection strategies as well as the fast and sensitive biochemical characterization approaches are highly demanded to identify new enzymes and utilize them. On the other hand, natural enzymes often need to be further optimized at molecular level to meet industrial and biotechnological requirements through protein engineering. Rational design, directed evolution, and computational design as three main tools have been used to tailor enzyme traits. In recent years, these tools have increasingly been combined to create focused and high quality mutant pools. New effective engineering approaches such as ISM and structure-guided recombination coupled with machine learning technique have been developed recently.82,128 As well, computational enzyme design has emerged as a promising tool for generating made-to-order biocatalysts. The low activities of designed enzymes can be further optimized by rational design and directed evolution approaches, clearly exemplified by two recent studies from the Hilvert group.17,18 Another significant advance in protein engineering that was not discussed in this review is the development and improvement of phage-assisted continuous evolution (PACE) in E. coli.129,130 Coupled with a suitable experiment design, the PACE may evolve a range of enzymes in a short time. A number of novel biocatalytic reactions have been discovered in the last few years. Some of these reactions were unprecedented, while the others might not occur in Nature at all.16,108,112,114–116,118 Further development of these novel biocatalysts will possibly create new opportunities for industrial applications. Given unparalleled virtues of biocatalysis, biocatalysts are leading to paradigm switches in many processes such as the production of pharmaceuticals. Consistent needs of robust, effective, stable, and specific biocatalysts for industrial processes underscore a systematic strategy (Fig. 1) to discover and develop novel biocatalysts. Newly gained knowledge through this strategy will be expected to further accelerate the expansion of practical biocatalysis applications. Acknowledgments This work was supported by the University of Florida startup program. We thank Professors Frances H. Arnold, Hendrik Luesch, Margaret James, Rosemary Loria, and Steven Bruner for their valuable suggestions and discussions on some contents of this review. References and notes 1. 2. 3. 4. 5. 6. 7. 8. 9.

10. 11. 12. 13. 14. 15. 16.

Wang, P. Appl. Biochem. Biotechnol. 2009, 152, 343. Tang, W. L.; Zhao, H. Biotechnol. J. 2009, 4, 1725. Wang, M.; Si, T.; Zhao, H. Bioresour. Technol. 2012, 115, 117. Fasan, R.; Chen, M. M.; Crook, N. C.; Arnold, F. H. Angew. Chem., Int. Ed. 2007, 46, 8414. Beloqui, A.; de Maria, P. D.; Golyshin, P. N.; Ferrer, M. Curr. Opin. Microbiol. 2008, 11, 240. Handelsman, J. Microbiol. Mol. Biol. Rev. 2004, 68, 669. Sommer, M. O.; Church, G. M.; Dantas, G. Mol. Syst. Biol. 2010, 6, 360. Fernandez-Arrojo, L.; Guazzaroni, M. E.; Lopez-Cortes, N.; Beloqui, A.; Ferrer, M. Curr. Opin. Biotechnol. 2010, 21, 725. Robertson, D. E.; Chaplin, J. A.; DeSantis, G.; Podar, M.; Madden, M.; Chi, E.; Richardson, T.; Milan, A.; Miller, M.; Weiner, D. P. Appl. Environ. Microbiol. 2004, 70, 2429. Wackett, L. P. Curr. Opin. Biotechnol. 2004, 15, 280. Lutz, S. Curr. Opin. Biotechnol. 2010, 21, 734. Höhne, M.; Schätzle, S.; Jochens, H.; Robins, K.; Bornscheuer, U. T. Nat. Chem. Biol. 2010, 6, 807. Toscano, M. D.; Woycechowsky, K. J.; Hilvert, D. Angew. Chem., Int. Ed. 2007, 46, 3212. Penning, T. M.; Jez, J. M. Chem. Rev. 2001, 101, 3027. Cobb, R. E.; Si, T.; Zhao, H. Curr. Opin. Chem. Biol. 2012, 16, 285. McIntosh, J. A.; Farwell, C. C.; Arnold, F. H. Curr. Opin. Chem. Biol. 2014, 19, 126.

5611

17. Blomberg, R.; Kries, H.; Pinkas, D. M.; Mittl, P. R.; Grutter, M. G.; Privett, H. K.; Mayo, S. L.; Hilvert, D. Nature 2013, 503, 418. 18. Giger, L.; Caner, S.; Obexer, R.; Kast, P.; Baker, D.; Ban, N.; Hilvert, D. Nat. Chem. Biol. 2013, 9, 494. 19. Hilvert, D. Annu. Rev. Biochem. 2013, 82, 447. 20. Bornscheuer, U.; Huisman, G.; Kazlauskas, R.; Lutz, S.; Moore, J.; Robins, K. Nature 2012, 485, 185. 21. Reetz, M. T. J. Am. Chem. Soc. 2013, 135, 12480. 22. Winter, J. M.; Behnken, S.; Hertweck, C. Curr. Opin. Chem. Biol. 2011, 15, 22. 23. Behrens, G. A.; Hummel, A.; Padhi, S. K.; Schätzle, S.; Bornscheuer, U. T. Adv. Synth. Catal. 2011, 353, 2191. 24. Ferrer, M.; Martínez-Abarca, F.; Golyshin, P. N. Curr. Opin. Biotechnol. 2005, 16, 588. 25. Schmeisser, C.; Steele, H.; Streit, W. R. Appl. Microbiol. Biotechnol. 2007, 75, 955. 26. Cox, M. J.; Schafer, H.; Nightingale, P. D.; McDonald, I. R.; Murrell, J. C. FEMS Microbiol. Lett. 2012, 334, 111. 27. Uchiyama, T.; Miyazaki, K. Curr. Opin. Biotechnol. 2009, 20, 616. 28. Rabausch, U.; Juergensen, J.; Ilmberger, N.; Böhnke, S.; Fischer, S.; Schubach, B.; Schulte, M.; Streit, W. Appl. Environ. Microbiol. 2013, 79, 4551. 29. Nacke, H.; Will, C.; Herzog, S.; Nowka, B.; Engelhaupt, M.; Daniel, R. FEMS Microbiol. Ecol. 2011, 78, 188. 30. Findley, S. D.; Mormile, M. R.; Sommer-Hurley, A.; Zhang, X.-C.; Tipton, P.; Arnett, K.; Porter, J. H.; Kerley, M.; Stacey, G. Appl. Environ. Microbiol. 2011, 77, 8106. 31. Wang, S.-d.; Guo, G.-s.; Li, L.; Cao, L.-c.; Tong, L.; Ren, G.-h.; Liu, Y.-h. Enzyme Microb. Technol. 2014, 26. 32. Mientus, M.; Brady, S.; Angelov, A.; Zimmermann, P.; Wemheuer, B.; Schuldes, J.; Daniel, R.; Liebl, W. Curr. Biotechnol. 2013, 2, 284. 33. Itoh, N.; Toda, H.; Matsuda, M.; Negishi, T.; Taniguchi, T.; Ohsawa, N. BMC Plant Biol. 2009, 9, 116. 34. Bayer, T. S.; Widmaier, D. M.; Temme, K.; Mirsky, E. A.; Santi, D. V.; Voigt, C. A. J. Am. Chem. Soc. 2009, 131, 6508. 35. Muanprasat, C.; Kaewmokul, S.; Chatsudthipong, V. Biol. Pharm. Bull. 2007, 30, 502. 36. Schafer, H.; McDonald, I. R.; Nightingale, P. D.; Murrell, J. C. Environ. Microbiol. 2005, 7, 839. 37. Lämmle, K.; Zipper, H.; Breuer, M.; Hauer, B.; Buta, C.; Brunner, H.; Rupp, S. J. Biotechnol. 2007, 127, 575. 38. Cheng, J.; Pinnell, L.; Engel, K.; Neufeld, J. D.; Charles, T. C. J. Microbiol. Methods 2014, 99, 27. 39. Iqbal, H. A.; Craig, J. W.; Brady, S. F. FEMS Microbiol. Lett. 2014, 19. 40. Hosokawa-Okamoto, R.; Miyazaki, K. In Metagenomics: Current Innovations and Future Trends; Horizon Scientific Press, 2011; p 241. 41. Taupp, M.; Mewis, K.; Hallam, S. J. Curr. Opin. Biotechnol. 2011, 22, 465. 42. Jiang, C.; Liu, Y.; Meng, C.; Wu, L.; Huang, J.; Deng, J.; Wang, J.; Shen, P.; Wu, B. Folia Microbiol. 2013, 58, 663. 43. Jiang, L.; Lin, M.; Zhang, Y.; Li, Y.; Xu, X.; Li, S.; He, H. PLoS ONE 2013, 8, e77437. 44. Parachin, N. S.; Gorwa-Grauslund, M. F. Biotechnol. Biofuels 2011, 4, 9. 45. Chen, R.; Li, C.; Pei, X.; Wang, Q.; Yin, X.; Xie, T. Indian J. Microbiol. 2014, 54, 74. 46. Jiang, C.; Yin, B.; Tang, M.; Zhao, G.; He, J.; Shen, P.; Wu, B. Antonie Van Leeuwenhoek 2013, 103, 1209. 47. Arima, J.; Isoda, Y.; Hatanaka, T.; Mori, N. World J. Microbiol. Biotechnol. 2013, 29, 899. 48. Lorenz, P.; Liebeton, K.; Niehaus, F.; Eck, J. Curr. Opin. Biotechnol. 2002, 13, 572. 49. Kim, B. S.; Kim, S. Y.; Park, J.; Park, W.; Hwang, K. Y.; Yoon, Y. J.; Oh, W. K.; Kim, B. Y.; Ahn, J. S. J. Appl. Microbiol. 2007, 102, 1392. 50. Rhew, R. C.; Ostergaard, L.; Saltzman, E. S.; Yanofsky, M. F. Curr. Biol. 2003, 13, 1809. 51. Kwoun Kim, H.; Jung, Y.-J.; Choi, W.-C.; Ryu, H. S.; Oh, T.-K.; Lee, J.-K. FEMS Microbiol. Lett. 2004, 235, 349. 52. McDonald, I. R.; Warner, K. L.; McAnulla, C.; Woodall, C. A.; Oremland, R. S.; Murrell, J. C. Environ. Microbiol. 2002, 4, 193. 53. Ohsawa, N.; Tsujita, M.; Morikawa, S.; Itoh, N. Biosci. Biotechnol. Biochem. 2001, 65, 2397. 54. Woodall, C. A.; Warner, K. L.; Oremland, R. S.; Murrell, J. C.; McDonald, I. R. Appl. Environ. Microbiol. 2001, 67, 1959. 55. Schomburg, I.; Chang, A.; Placzek, S.; Söhngen, C.; Rother, M.; Lang, M.; Munaretto, C.; Ulas, S.; Stelzer, M.; Grote, A. NAR 2013, 41, D764. 56. Attieh, J.; Sparace, S. A.; Saini, H. S. Arch. Biochem. Biophys. 2000, 380, 257. 57. Coulter, C.; Hamilton, J. T.; McRoberts, W. C.; Kulakov, L.; Larkin, M. J.; Harper, D. B. Appl. Environ. Microbiol. 1999, 65, 4301. 58. Ni, X.; Hager, L. P. Proc. Natl. Acad. Sci. U.S.A. 1999, 96, 3611. 59. Sorensen, J. B.; Larsen, E. H. J. Gen. Physiol. 1998, 112, 19. 60. Zhao, S.; Kumar, R.; Sakai, A.; Vetting, M. W.; Wood, B. M.; Brown, S.; Bonanno, J. B.; Hillerich, B. S.; Seidel, R. D.; Babbitt, P. C. Nature 2013, 502, 698. 61. Kreimeyer, A.; Perret, A.; Lechaplais, C.; Vallenet, D.; Médigue, C.; Salanoubat, M.; Weissenbach, J. J. Biol. Chem. 2007, 282, 7191. 62. Bellinzoni, M.; Bastard, K.; Perret, A.; Zaparucha, A.; Perchat, N.; Vergne, C.; Wagner, T.; de Melo-Minardi, R. C.; Artiguenave, F.; Cohen, G. N. J. Biol. Chem. 2011, 286, 27399. 63. Bastard, K.; Smith, A. A. T.; Vergne-Vaxelaire, C.; Perret, A.; Zaparucha, A.; De Melo-Minardi, R.; Mariage, A.; Boutard, M.; Debard, A.; Lechaplais, C. Nat. Chem. Biol. 2014, 10, 42. 64. Böttcher, D.; Bornscheuer, U. T. Curr. Opin. Microbiol. 2010, 13, 274.

5612 65. 66. 67. 68. 69. 70. 71. 72. 73. 74. 75. 76. 77. 78. 79. 80. 81. 82. 83. 84. 85. 86. 87. 88. 89.

90. 91. 92. 93. 94. 95. 96. 97.

G. Yang, Y. Ding / Bioorg. Med. Chem. 22 (2014) 5604–5612 Bornscheuer, U. T.; Pohl, M. Curr. Opin. Chem. Biol. 2001, 5, 137. Chica, R. A.; Doucet, N.; Pelletier, J. N. Curr. Opin. Biotechnol. 2005, 16, 378. Bolon, D. N.; Voigt, C. A.; Mayo, S. L. Curr. Opin. Chem. Biol. 2002, 6, 125. Yang, G.; De Santi, C.; de Pascale, D.; Pucciarelli, S.; Pucciarelli, S.; Miceli, C. Biochimie 2013, 95, 1795. Livesey, J. C.; Anders, M. W. Drug Metab. Dispos. 1979, 7, 199. Jackel, C.; Bloom, J. D.; Kast, P.; Arnold, F. H.; Hilvert, D. J. Mol. Biol. 2010, 399, 541. Sullivan, B. J.; Nguyen, T.; Durani, V.; Mathur, D.; Rojas, S.; Thomas, M.; Syu, T.; Magliery, T. J. J. Mol. Biol. 2012, 420, 384. Cadwell, R. C.; Joyce, G. F. Genome Res. 1992, 2, 28. Kretz, K. A.; Richardson, T. H.; Gray, K. A.; Robertson, D. E.; Tan, X.; Short, J. M. Methods Enzymol. 2004, 388, 3. Stemmer, W. P. Nature 1994, 370, 389. Dalby, P. A. Curr. Opin. Struct. Biol. 2011, 21, 473. Cobb, R. E.; Chao, R.; Zhao, H. AIChE J. 2013, 59, 1432. Bougioukou, D. J.; Kille, S.; Taglieber, A.; Reetz, M. T. Adv. Synth. Catal. 2009, 351, 3287. Reetz, M. T.; Prasad, S.; Carballeira, J. D.; Gumulya, Y.; Bocola, M. J. Am. Chem. Soc. 2010, 132, 9144. Prasad, S.; Bocola, M.; Reetz, M. T. ChemPhysChem 2011, 12, 1550. Parra, L. P.; Agudo, R.; Reetz, M. T. ChemBioChem 2013, 14, 2301. Reetz, M. T.; Soni, P.; Fernández, L.; Gumulya, Y.; Carballeira, J. D. Chem. Commun. 2010, 45, 8657. Romero, P. A.; Krause, A.; Arnold, F. H. Proc. Natl. Acad. Sci. U.S.A. 2013, 110, E193. Granieri, L.; Baret, J.-C.; Griffiths, A. D.; Merten, C. A. Chem. Biol. 2010, 17, 229. Thorsen, T.; Maerkl, S. J.; Quake, S. R. Science 2002, 298, 580. Benson, D. E.; Wisz, M. S.; Hellinga, H. W. Proc. Natl. Acad. Sci. U.S.A. 2000, 97, 6292. Benson, D. E.; Haddy, A. E.; Hellinga, H. W. Biochemistry 2002, 41, 3262. Hill, R. B.; Raleigh, D. P.; Lombardi, A.; DeGrado, W. F. Acc. Chem. Res. 2000, 33, 745. Siegel, J. B.; Zanghellini, A.; Lovick, H. M.; Kiss, G.; Lambert, A. R.; Clair, J. L. S.; Gallaher, J. L.; Hilvert, D.; Gelb, M. H.; Stoddard, B. L. Science 2010, 329, 309. Röthlisberger, D.; Khersonsky, O.; Wollacott, A. M.; Jiang, L.; DeChancie, J.; Betker, J.; Gallaher, J. L.; Althoff, E. A.; Zanghellini, A.; Dym, O. Nature 2008, 453, 190. Jiang, L.; Althoff, E. A.; Clemente, F. R.; Doyle, L.; Röthlisberger, D.; Zanghellini, A.; Gallaher, J. L.; Betker, J. L.; Tanaka, F.; Barbas, C. F. Science 2008, 319, 1387. Baker, D. Protein Sci. 2010, 19, 1817. Richter, F.; Leaver-Fay, A.; Khare, S. D.; Bjelic, S.; Baker, D. PLoS ONE 2011, 6, e19230. Khersonsky, O.; Kiss, G.; Röthlisberger, D.; Dym, O.; Albeck, S.; Houk, K. N.; Baker, D.; Tawfik, D. S. Proc. Natl. Acad. Sci. U.S.A. 2012, 109, 10358. de Regil, R.; Sandoval, G. Biomolecules 2013, 3, 812. Hanefeld, U. Org. Biomol. Chem. 2003, 1, 2405. Bornscheuer, U. T.; Kazlauskas, R. J.; Brakmann, S.; Johnsson, K. In Modern Biooxidation; Wiley-VCH GmbH & Co. KGaA, 2007; p 300. Turner, N. J.; Truppo, M. D. In Chiral Amine Synthesis; Wiley-VCH GmbH & Co. KGaA, 2010; p 431.

98. Strohmeier, G. A.; Pichler, H.; May, O.; Gruber-Khadjawi, M. Chem. Rev. 2011, 111, 4141. 99. Höhne, M.; Bornscheuer, U. T. ChemCatChem 2009, 1, 42. 100. Perret, A.; Lechaplais, C.; Tricot, S.; Perchat, N.; Vergne, C.; Pelle, C.; Bastard, K.; Kreimeyer, A.; Vallenet, D.; Zaparucha, A.; Weissenbach, J.; Salanoubat, M. PLoS ONE 2011, 6, e22918. 101. Savile, C. K.; Janey, J. M.; Mundorff, E. C.; Moore, J. C.; Tam, S.; Jarvis, W. R.; Colbeck, J. C.; Krebber, A.; Fleitz, F. J.; Brands, J. Science 2010, 329, 305. 102. Midelfort, K. S.; Kumar, R.; Han, S.; Karmilowicz, M. J.; McConnell, K.; Gehlhaar, D. K.; Mistry, A.; Chang, J. S.; Anderson, M.; Villalobos, A.; Minshull, J.; Govindarajan, S.; Wong, J. W. Protein Eng. Des. Sel. 2013, 26, 25. 103. Guengerich, F. P.; Munro, A. W. J. Biol. Chem. 2013, 288, 17065. 104. Guengerich, F. P. Chem. Res. Toxicol. 2001, 14, 611. 105. Podust, L. M.; Sherman, D. H. Nat. Prod. Rep. 2012, 29, 1251. 106. Whitehouse, C. J.; Bell, S. G.; Wong, L.-L. Chem. Soc. Rev. 2012, 41, 1218. 107. Jung, S. T.; Lauchli, R.; Arnold, F. H. Curr. Opin. Biotechnol. 2011, 22, 809. 108. Barry, S. M.; Kers, J. A.; Johnson, E. G.; Song, L. J.; Aston, P. R.; Patel, B.; Krasnoff, S. B.; Crane, B. R.; Gibson, D. M.; Loria, R.; Challis, G. L. Nat. Chem. Biol. 2012, 8, 814. 109. Yan, G. B.; Yang, M. H. Org. Biomol. Chem. 2013, 11, 2554. 110. Parry, R.; Nishino, S.; Spain, J. Nat. Prod. Rep. 2011, 28, 152. 111. Kersten, R. D.; Dorrestein, P. C. Nat. Chem. Biol. 2010, 6, 636. 112. Matthews, M. L.; Chang, W. C.; Layne, A. P.; Miles, L. A.; Krebs, C.; Bollinger, J. M., Jr. Nat. Chem. Biol. 2014, 10, 209. 113. Wolf, J. R.; Hamaker, C. G.; Djukic, J. P.; Kodadek, T.; Woo, L. K. J. Am. Chem. Soc. 1995, 117, 9194. 114. Coelho, P. S.; Brustad, E. M.; Kannan, A.; Arnold, F. H. Science 2013, 339, 307. 115. Coelho, P. S.; Wang, Z. J.; Ener, M. E.; Baril, S. A.; Kannan, A.; Arnold, F. H.; Brustad, E. M. Nat. Chem. Biol. 2014, 10, 164. 116. Wang, Z. J.; Peck, N. E.; Renata, H.; Arnold, F. H. Chem. Sci. 2014, 5, 598. 117. McIntosh, J. A.; Coelho, P. S.; Farwell, C. C.; Wang, Z. J.; Lewis, J. C.; Brown, T. R.; Arnold, F. H. Angew. Chem., Int. Ed. 2013, 52, 9309. 118. Singh, R.; Bordeaux, M.; Fasan, R. ACS Catal. 2014, 4, 546. 119. Kayser, M. M. Tetrahedron 2009, 65, 947. 120. Zhang, Z. G.; Parra, L. P.; Reetz, M. T. Chemistry 2012, 18, 10160. 121. Balke, K.; Kadow, M.; Mallin, H.; Sass, S.; Bornscheuer, U. T. Org. Biomol. Chem. 2012, 10, 6249. 122. Singh, A.; Singh Chauhan, N.; Thulasiram, H. V.; Taneja, V.; Sharma, R. Bioresour. Technol. 2010, 101, 8481. 123. Szolkowy, C.; Eltis, L. D.; Bruce, N. C.; Grogan, G. ChemBioChem 2009, 10, 1208. 124. Rebehmed, J.; Alphand, V.; de Berardinis, V.; de Brevern, A. G. Biochimie 2013, 95, 1394. 125. Rodríguez, C.; de Gonzalo, G.; Fraaije, M. W.; Gotor, V. Tetrahedron: Asymmetry 2007, 18, 1338. 126. van Beek, H. L.; de Gonzalo, G.; Fraaije, M. W. Chem. Commun. 2012, 3288. 127. van Beek, H. L.; Wijma, H. J.; Fromont, L.; Janssen, D. B.; Fraaije, M. W. FEBS Open Biol. 2014, 4, 168. 128. Reetz, M. T.; Carballeira, J. D. Nat. Protoc. 2007, 2, 891. 129. Carlson, J. C.; Badran, A. H.; Guggiana-Nilo, D. A.; Liu, D. R. Nat. Chem. Biol. 2014, 10, 216. 130. Esvelt, K. M.; Carlson, J. C.; Liu, D. R. Nature 2011, 472, 499.

Recent advances in biocatalyst discovery, development and applications.

Enzymes catalyze a wide range of biotransformations and have a great potential as environmentally friendly alternatives to classical chemical catalyst...
1MB Sizes 2 Downloads 4 Views