|Ushimaru R, Liu HW.
|Biosynthetic Origin of the Atypical Stereochemistry in the Thioheptose Core of Albomycin Nucleoside Antibiotics
|J Am Chem Soc
|Albomycins are peptidyl thionucleoside natural products that display antimicrobial activity against clinically important patho-gens. Their structures are characterized by a thioheptose with atypical stereochemistry including a D-xylofuranose ring modified with a D-amino acid moiety. Herein it is demonstrated that AbmH is a pyridoxal 5'-phosphate (PLP)-dependent transal-dolase that catalyzes a threo-selective aldol-type reaction to gener-ate the thioheptose core with a D-ribofuranose ring and an L-amino acid moiety. The conversion of L- to D-amino acid con-figuration is catalyzed by the PLP-dependent epimerase AbmD. The D-ribo to D-xylo conversion of the thiofuranose ring appears according to gene deletion experiments to be mediated by AbmJ, which is annotated as a radical S-adenosyl-L-methionine (SAM) enzyme. These studies establish several key steps in the as-sembly of the thioheptose core during the biosynthesis of albomycins.