Biocatalytic asymmetric synthesis of chiral amines from ketones applied to sitagliptin manufacture

Science

Volumn 329, Issue 5989, 2010, Pages 305-309

  Savile, Christopher K ^a   Janey, Jacob M ^b   Mundorff, Emily C ^a   Moore, Jeffrey C ^b   Tam, Sarena ^a   Jarvis, William R ^a   Colbeck, Jeffrey C ^a   Krebber, Anke ^a   Fleitz, Fred J ^b   Brands, Jos ^b   Devine, Paul N ^b   Huisman, Gjalt W ^a   Hughes, Gregory J ^b  

^a R and D Project Development and Management   (United States)

^b MERCK RESEARCH LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMINE; AMINOTRANSFERASE; ENAMINE; KETONE DERIVATIVE; RHODIUM; SITAGLIPTIN;

ASYMMETRY; BIOENGINEERING; CATALYSIS; DRUG; ECONOMIC ANALYSIS; ENZYME ACTIVITY; KETONE; MUTATION; RESOLUTION;

ARTICLE; ASYMMETRIC SYNTHESIS; BIOCATALYSIS; BIOCATALYST; CHIRALITY; DRUG MANUFACTURE; DRUG SYNTHESIS; ECONOMIC ASPECT; HYDROGENATION; LARGE SCALE PRODUCTION; PRIORITY JOURNAL;

AMINES; BIOCATALYSIS; CATALYTIC DOMAIN; DIRECTED MOLECULAR EVOLUTION; HYPOGLYCEMIC AGENTS; KETONES; MODELS, MOLECULAR; MOLECULAR STRUCTURE; MUTAGENESIS; PROTEIN CONFORMATION; PROTEIN ENGINEERING; PYRAZINES; SOLUBILITY; STEREOISOMERISM; SUBSTRATE SPECIFICITY; TRANSAMINASES; TRIAZOLES;

EID: 77954797329     PISSN: 00368075     EISSN: 10959203     Source Type: Journal    
DOI: 10.1126/science.1188934     Document Type: Article

References (33)

1. N. B. Johnson, I. C. Lennon, P. H. Moran, J. A. Ramsden, Acc. Chem. Res. 40, 1291 (2007).
2. D. M. Kendall, R. M. Cuddihy, R. M. Bergenstal, Eur. J. Intern. Med. 20 (suppl.), S329 (2009).
3. D. Williams-Herman et al., BMC Endocr. Disord. 8, 14 (2008).
4. K. B. Hansen et al., J. Am. Chem. Soc. 131, 8798 (2009).
5. α-Transaminases are pyridoxal 5′-phosphate (PLP)-dependent enzymes widespread in nature for the synthesis of α-amino acids from the corresponding α-keto acids; comparatively few ω-transaminases, for the synthesis of chiral amines that are not adjacent to carboxylic acid functionalities, are known.
6. S. P. Crump, J. D. Rozzell, in Biocatalytie Production of Amino Acids and Derivatives, J. D. Rozzell, F. Wagner, Eds. (Wiley, New York, 1992), pp. 43-58.
7. J.-S. Shin, B.-G. Kim J. Org. Chem. 67, 2848 (2002).
8. B.-K. Cho et al., Biotechnol. Bioeng. 99, 275 (2008).
9. M. Höhne, S. Kühl, K. Robins, U. T. Bornscheuer, ChemBioChem 9, 363 (2008).
10. M. D. Truppo, J. D. Rozzell, J. C Moore, N. J. Turner, Org. Biomol. Chem. 7, 395 (2009).
11. M. D. Truppo, N. J. Turner, J. D. Rozzell, Chem. Commun. 2009, 2127 (2009).
12. D. Koszelewski, D. Clay, D. Rozzell, W. Kroutil, Eur. J. Org. Chem. 2009, 2289 (2009).
13. D. Koszelewski et al., Angew. Chem. Int. Ed. 47, 9337 (2008).
14. D. Koszelewski, I. Lavandera, D. Clay, D. Rozzell, W. Kroutil, Adv. Synth. Catal. 350, 2761 (2008).
15. The complete amino acid sequence of ATA-117 is as follows: MAFSADTSEIVYTHDTGLDYITYSDYELDPANPLAGGAAWIEGAFVPPSEARISIFDQGYLHSDVTYTVFHVWNGNAFR LDDHIERLFSNAESMRIIPPLTQDEVKEIALELVAKTELREAFVSVSITRGYSSTPGERDITKHRPQVYMYAVPYOWIV PFDRIRDGVHAMVAQSVRRTPRSSIDPQVKNFQWGDURAVQETHDRGFEAPLLLDGDGLLAEGSGFNVWIKDGWRSPGR AALPGITRKTVLEIAESLGHEAILADITLAELLDADEVLGCTTAGGVWPFVSVDGNPISDGVPGPVTQSIIRRYWELNV ESSSLLTPVQY.
16. A. Iwasaki, Y. Yamada, N. Kizaki, Y. Ikenaka, J. Hasegawa, Appl. Microbiol. Biotechnol. 69, 499 (2006).
17. Materials and methods are detailed in supporting online material on Science Online.
18. Z. Chen, H. Zhao, J. Mol. Biol. 348, 1273 (2005).
19. Single-letter abbreviations for the amino acid residues are as follows: A, Ala; C, Cys; D, Asp; E, Glu; F, Phe; G, Gly; H, His; I, Ile; K, Lys; L, Leu; M, Met; N, Asn; P, Pro; 0, Gln; R, Arg; S, Ser; T, Thr; V, Val; W, Trp; and Y, Tyr.
20. G. W. Huisman, J. J. Lalonde, in Biocatalysis in the Pharmaceutical and Biotechnology Industries, R. N. Patel, Ed. (CRC, Boca Raton, FL, 2006), pp. 717-742.
21. I. W. Davies, C. J. Welch, Science 325, 701 (2009).
22. R. J. Fox et al., Nat. Biotechnol. 25, 338 (2007).
23. J. H. Zhang, G. Dawes, W. P. Stemmer, Proc. Natl. Acad. Sci. U.S.A. 94, 4504 (1997).
24. K. Stutzman-Engwall et al., Metab. Eng. 7, 27 (2005).
25. J. Liao et al., BMC Biotechnol. 7, 16 (2007).
26. See "quantitation of catalyst improvement," figs. S1 and S2, and tables S10 and S11 in supporting online material (SOM) on Science Online.
27. Size exclusion chromatography data show the enzyme forms a dimer (fig. S4).
28. V. G. H. Eijsink et al., J. Biotechnol. 113, 105 (2004).
29. D. J. C Constable et al., Green Chem. 9, 411 (2007).
30. S. M. A. De Wildeman, T. Sonke, H. E. Schoemaker, O. May, Acc. Chem. Res. 40, 1260 (2007).
31. J. C. Moore, D. J. Pollard, B. Kosjek, P. N. Devine, Acc. Chem. Res. 40, 1412 (2007).
32. G. W. Huisman, J. Liang, A. Krebber, Curr. Opin. Chem. Biol. 14, 122 (2010).
33. We thank C. Ng, D. Standish, M. Mayhew, D. Gray, C. Fletcher, F. Mazzini, P. Lattik, T. Brandon, and J. Postlethwaite for developing the transaminase production system; R. Fox for bioinformatics support; M. Jefferson, R. Trinidad, and M. Whitehorn for assay support; V. Mitchell for molecular biology support; J. Munger and O. Gooding for process development support; P. Fernandez, S. Grosser, and M. Mohan for pilot scale development; K. Morley and B. Grau for additional synthesis support; M. Foster and N. Wu for analytical support; and L. Moore, S. Lato, P. Seufer-Wasserthal, J. Grate, J. Liang, and J. Lalonde for helpful suggestions. Merck and Codexis have filed patent applications on the transaminases, the genes encoding them as well as their use. Materials can be provided under a materials transfer agreement; requests for enzymes should be directed to C.K.S. (christopher.savile@ codexis.com), whereas requests for substrates, products, and process information should be directed to J.M.J. (jacob-janey@merck.com).