Biocatalytic Synthesis of α-Amino Ketones

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

Key words

biocatalysis - biosynthesis - α-oxoamine synthases - neurotoxins - α-amino ketones - pyridoxal-5′-phosphate

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