Characterization of a novel type of oxidative decarboxylase involved in the biosynthesis of the styryl moiety of chondrochloren from an acylated tyrosine.

Myxobacteria are soil-dwelling bacteria notable for several unique behavioral features, such as cellular movement by gliding and the formation of multicellular fruiting bodies. More recently they have gained recognition as producers of several unique polyketide and nonribosomal polypeptide metabolites with potential therapeutic value. The biosynthesis of these compounds often involves highly unusual mechanisms including the formation of the chloro-hydroxy-styryl moiety of the chondrochloren antibiotic produced by Chondromyces crocatus Cm c5. Here it is shown that the final product of the chondrochloren megasynthetase is the novel natural product pre-chondrochloren, a carboxylated and saturated derivative of chondrochloren. This compound was isolated from strains harboring mutants of a hypothetical oxidative decarboxylase (CndG) identified in the chondrochloren gene cluster. CndG was heterologously expressed in Escherichia coli and shown to be an FAD-dependent oxidative decarboxylase. Biochemical characterization of the protein was achieved using the intermediate described above as the substrate and yielded chondrochloren by oxidative decarboxylation. It was also demonstrated that the CndG post-assembly line modification of pre-chondrochloren is essential for the biological activity of chondrochloren.