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
