Furan and Lactam Jadomycin Biosynthetic Congeners Isolated from Streptomyces venezuelae ISP5230 Cultured with Nε‑Trifluoroacetyl‑l‑lysine
journal contributionposted on 18.05.2017, 19:13 authored by Stephanie M. Forget, Andrew W. Robertson, David P. Overy, Russell G. Kerr, David L. Jakeman
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 Nε-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 15Nα- or 15Nε-lysine demonstrated the incorporation of Nα 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.
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Gram-positive bacteriaring-opened formfour-ring angularlyjadomycin biosynthesisjadomycin N εDifferential cyclization chemistryangucycline backboneamide functionalitiestandem mass spectrometry analysiscancer cell panelscongenerBiosynthetic incorporationStreptomyces venezuelae ISP 5230 Culturedfuran analoguesLactam Jadomycin Biosynthetic Congeners15 N ε15 N αN αStreptomyces venezuelae ISP 5230 culturesNMR spectroscopyTFALpolyaromatic backbone