Biosynthetic Origin of the Atypical Stereochemistry in the Thioheptose Core of Albomycin Nucleoside Antibiotics

Albomycins are peptidyl thionucleoside
natural products that display
antimicrobial activity against clinically important pathogens. 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 transaldolase that catalyzes a threo-selective aldol-type reaction to generate the thioheptose
core with a d-ribofuranose ring and an l-amino acid
moiety. The conversion of l-to d-amino acid configuration
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 assembly of the thioheptose core during the
biosynthesis of albomycins.