Furan and Lactam Jadomycin Biosynthetic Congeners Isolated from Streptomyces venezuelae ISP5230 Cultured with Nε-Trifluoroacetyl-l-lysine.
Stephanie M ForgetAndrew W RobertsonDavid P OveryRussell G KerrDavid L JakemanPublished in: Journal of natural products (2017)
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.
Keyphrases
- tandem mass spectrometry
- ultra high performance liquid chromatography
- high performance liquid chromatography
- liquid chromatography
- gas chromatography
- gram negative
- simultaneous determination
- amino acid
- small molecule
- high resolution
- staphylococcus aureus
- solid phase extraction
- mass spectrometry
- molecular docking
- high throughput
- hydrogen peroxide
- high resolution mass spectrometry
- adipose tissue
- multidrug resistant
- blood glucose
- ms ms
- nitric oxide
- plant growth
- single cell
- glycemic control