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DOI: 10.1055/s-0037-1611755
Biocatalytic Synthesis of α-Amino Ketones
This research was supported by funds from the University of Michigan Life Sciences Institute and the National Institute of General Medical Sciences of the National Institutes of Health (R35 GM124880).
Publication History
Received: 04 February 2019
Accepted after revision: 18 February 2019
Publication Date:
19 March 2019 (online)
Abstract
Stereospecific generation of α-amino ketones from common α-amino acids is difficult to achieve, often employing superstoichiometric alkylating reagents and requiring multiple protecting group manipulations. In contrast, the α-oxoamine synthase protein family performs this transformation stereospecifically in a single step without the need for protecting groups. Herein, we detail the characterization of the 8-amino-7-oxononanoate synthase (AONS) domain of the four-domain polyketide-like synthase SxtA, which natively mediates the formation of the ethyl ketone derivative of arginine. The function of each of the four domains is elucidated, leading to a revised proposal for the initiation of saxitoxin biosynthesis, a potent neurotoxin. We also demonstrate the synthetic potential of SxtA AONS, which is applied to the synthesis of a panel of novel α-amino ketones.
1 Introduction
2 Native SxtA Module Activity
3 New Reactions with SxtA AONS
4 Conclusions and Outlook
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References
- 1 Eliot AC, Kirsch JF. Annu. Rev. Biochem. 2004; 73: 383
- 2 Boville CE, Scheele RA, Koch P, Brinkmann-Chen S, Buller AR, Arnold FH. Angew. Chem. Int. Ed. 2018; 9: 14764
- 3 Steffen-Munsberg F, Vickers C, Kohls H, Land H, Mallin H, Nobili A, Skalden L, van den Bergh T, Joosten H.-J, Berglund P, Höhne M, Bornscheuer UT. Biotechnol. Adv. 2015; 33: 566
- 4 Webster SP, Alexeev D, Campopiano DJ, Watt RM, Alexeeva M, Sawyer L, Baxter RL. Biochemistry 2000; 39: 516
- 5 Yard BA, Carter LG, Johnson KA, Overton IM, Dorward M, Liu H, McMahon SA, Oke M, Puech D, Barton GJ, Naismith JH, Campopiano DJ. J. Mol. Biol. 2007; 370: 870
- 6 Chun SW, Hinze ME, Skiba MA, Narayan AR. H. J. Am. Chem. Soc. 2018; 140: 2430
- 7 Kellmann R, Mihali TK, Young JJ, Pickford R, Pomati F, Neilan BA. Appl. Environ. Microbiol. 2008; 74: 4044
- 8 Staunton J, Weissman KJ. Nat. Prod. Rep. 2001; 18: 380
- 9 Mihali TK, Kellmann R, Neilan BA. BMC Biochem. 2009; 10: 8
- 10 Mihali TK, Carmichael WW, Neilan BA. PLoS One 2011; 6: e14657
- 11 Shimizu Y. Chem. Rev. 1993; 93: 1685
- 12 Tsuchiya S, Cho Y, Konoki K, Nagasawa K, Oshima Y, Yotsu-Yamashita M. Sci. Rep. 2016; 6: 20340
- 13 Fesko K. Appl. Genet. Mol. Biotechnol. 2016; 100: 2579
- 14 Duff SM. G, Rydel TJ, Mcclerren AL, Zhang W, Li JY, Sturman EJ, Halls C, Chen S, Zeng J, Peng J, Kretzler CN, Evdokimov A. Arch. Biochem. Biophys. 2012; 528: 90
- 15 Lemagueres P, Im H, Dvorak A, Strych U, Benedik M, Krause KL. Biochemistry 2003; 42: 14752
- 16 Komori H, Nitta Y, Ueno H, Higuchi Y. J. Biol. Chem. 2012; 287: 29175
- 17 Schneider TR, Gerhardt E, Lee M, Liang P, Anderson KS, Schlichting I. Biochemistry 1998; 37: 5394
- 18 Clifton MC, Abendroth J, Edwards TE, Leibly DJ, Gillespie AK, Ferrell M, Dieterich SH, Exley I, Staker BL, Myler PJ, Van Voorhis WC, Stewart LJ. Acta Crystallogr., Sect. F: Struct. Biol. Cryst. Commun. 2011; 67: 1154
- 19 Pfeifer BA, Admiraal SJ, Gramajo H, Cane DE, Khosla C. Science 2001; 291: 1790
- 20 Gu L, Geders TW, Wang B, Gerwick WH, Hakansson K, Smith JL, Sherman DH. Science 2007; 318: 970
- 21 Skiba MA, Sikkema AP, Moss NA, Tran CL, Sturgis RM, Gerwick L, Gerwick WH, Sherman DH, Smith JL. ACS Chem. Biol. 2017; 12: 3039
- 22 Keatinge-Clay AT. Chem. Rev. 2017; 117: 5334
- 23 Dorrestein PC, Bumpus SB, Calderone CT, Garneau-Tsodikova S, Aron ZD, Straight PD, Kolter R, Walsh CT, Kelleher NL. Biochemistry 2006; 45: 12756
- 24 Quadri LE, Weinreb PH, Lei M, Nakano MM, Zuber P, Walsh CT. Biochemistry 1998; 37: 1585
- 25 Liu X, Sheng J, Curtiss III R. Proc. Natl. Acad. Sci. U.S.A. 2011; 108: 6899
- 26 Astner I, Schulze JO, Van Den Heuvel J, Jahn D, Schubert WD, Heinz DW. EMBO J. 2005; 24: 3166
- 27 Schmidt A, Sivaraman J, Li Y, Larocque R, Barbosa JA. R. G, Smith C, Matte A, Schrag JD, Cygler M. Biochemistry 2001; 40: 5151
- 28 Garneau-Tsodikova S, Dorrestein PC, Kelleher NL, Walsh CT. J. Am. Chem. Soc. 2006; 128: 12600
- 29 Manandhar M, Cronan JE. Appl. Environ. Microbiol. 2018; 84: e02084-17
- 30 Fisher LE, Muchowski JM. Org. Prep. Proced. Int. 1990; 22: 399
- 31 Sheppard GS, Florjancic AS. Synthesis 2003; 1653
- 32 Liebeskind LS, Yang H, Li H. Angew. Chem. 2009; 121: 1445
- 33 Hansen DA, Koch AA, Sherman DH. J. Am. Chem. Soc. 2015; 137: 3735