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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).Publikationsverlauf
Received: 04. Februar 2019
Accepted after revision: 18. Februar 2019
Publikationsdatum:
19. März 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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