Furan and Lactam Jadomycin Biosynthetic Congeners Isolated from <i>Streptomyces venezuelae</i> ISP5230 Cultured with <i>N</i>_ε-Trifluoroacetyl-<scp>l</scp>-lysine

Abstract

Angucycline antibiotics are composed of a classical four-ring angularly linked polyaromatic backbone. Differential cyclization chemistry of the A- and B-rings in jadomycin biosynthesis led to the discovery of two new furan analogues, while oxidation led to a ring-opened form of the jadomycin N_ε-trifluoroacetyl-l-lysine (TFAL) congener. The compounds were isolated from Streptomyces venezuelae ISP5230 cultures grown with TFAL. Biosynthetic incorporation using d-[1-¹³C]-glucose in cultures enabled the unambiguous assignment of the aldehyde, alcohol, and amide functionalities present in these new congeners through NMR spectroscopy. Tandem mass spectrometry analysis of cultures grown with ¹⁵N_α- or ¹⁵N_ε-lysine demonstrated the incorporation of N_α exclusively into the angucycline backbone, contrasting results with ornithine [J. Am. Chem. Soc. 2015, 137, 3271]. Compounds were evaluated against antimicrobial and cancer cell panels and found to possess good activity against Gram-positive bacteria.