Antibacterial and Antifungal Polyketides from Environmental Amycolatopsis Strains

This technology includes three new chemical entities discovered for antibacterial and antifungal activities. The compounds are novel tetramic acid containing polyketides obtained from two different Amycolatopsis strains. Their planar structures and relative stereochemistry were elucidated by 1D and 2D NMR methods, including 1H-1H and 13C-13C COSY, TOCSY, HSQC, HMBC and ROESY. Whole genome sequencing of these two strains revealed a 158 kb biosynthetic gene cluster (BGC) containing a 23-module, mixed NRPS-PKS pathway responsible for their biosynthesis. Glycosylation appears to be a self-protection mechanism based on the activities of a glycosyltransferase and secreted glycosyl hydrolase encoded in the BGC. Databases show the closest related compounds are blasticidin A and aflastatin A. However, our compound has a different molecular weight, different hydroxylation patterns, and an unsaturated C-8 starter unit. These changes are significant in terms of chemical space and biological activity.