SorF: a glycosyltransferase with promiscuous donor substrate specificity in vitro.

Glycosylations are well-established steps in numerous biosynthetic pathways, and the attached sugar moieties often influence the specificity or pharmacology of the modified compounds. The sorangicins belong to the polyketide family of natural products, and exhibit antibiotic activity through inhibition of bacterial RNA polymerase. We have identified the sorangicin biosynthetic gene cluster in the producing myxobacterium Sorangium cellulosum So ce12.

Nucleotide deoxysugars: essential tools for the glycosylation engineering of novel bioactive compounds.

The irreversible spread of new resistance mechanisms against existing therapeutical antibiotics has led to the development of technologies and strategies for the glycosylation engineering of novel antibiotics. Amino-, C-branched and O-methylated 6-deoxyhexoses play a favourite role in the biosynthesis of clinically important antibiotics like tylosin, erythromycin or oleandomycin and are essential for the antibiotic activity. They are transferred onto the aglycon by glycosyltransferases using dTDP-activated deoxyhexoses.

An enzyme module system for the synthesis of dTDP-activated deoxysugars from dTMP and sucrose.

A flexible enzyme module system is presented that allows preparative access to important dTDP-activated deoxyhexoses from dTMP and sucrose. The strategic combination of the recombinant enzymes dTMP-kinase and sucrose synthase (SuSy), and the enzymes RmlB (4,6-dehydratase), RmlC (3,5-epimerase) and RmlD (4-ketoreductase) from the biosynthetic pathway of dTDP-beta-L-rhamnose was optimized. The SuSy module (dTMP-kinase, SuSy, +/-RmlB) yielded the precursor dTDP-alpha-D-glucose (2) or the biosynthetic intermediate dTDP-6-deoxy-4-keto-alpha-D-glucose (3) on a 0.