Hamuramicin C, a Cytotoxic Bicyclic Macrolide Isolated from a Wasp Gut Bacterium

• Published in: Journal of natural products (Washington, D.C.) Vol. 85; no. 4; pp. 936 - 942
• Main Authors: An, Joon Soo, Lim, Hyung-Ju, Lee, Ji Yun, Jang, Yong-Joon, Nam, Sang-Jip, Lee, Sang Kook, Oh, Dong-Chan
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society and American Society of Pharmacognosy 22.04.2022
• Subjects: Animals; Anti-Bacterial Agents - chemistry; Antineoplastic Agents - metabolism; Antineoplastic Agents - pharmacology; Humans; Macrolides - chemistry; Molecular Structure; Polyketide Synthases - metabolism; Streptomyces - chemistry; Wasps
• ISSN: 0163-3864; 1520-6025
• DOI: 10.1021/acs.jnatprod.1c01075

A new bicyclic macrolide, hamuramicin C (1), was isolated from Streptomyces sp. MBP16, a gut bacterial strain of the wasp Vespa crabro flavofasciata. Its 22-membered macrocyclic lactone structure was determined by NMR and mass spectrometry. The relative configurations of hamuramicin C (1) were assigned by J-based configuration analysis utilizing 1H rotating frame Overhauser effect spectroscopy and heteronuclear long-range coupling NMR spectroscopy. Genomic and bioinformatic analyses of the bacterial strain enabled identification of the type-I polyketide synthase pathway, which employs a trans-acyltransferase system. The absolute configurations of 1 were proposed based on the analysis of the sequences of ketoreductases in the modular gene cluster. Moreover, hamuramicin C (1) demonstrated significant inhibitory activity against diverse human cancer cell lines (HCT116, A549, SNU-638, SK-HEP-1, and MDA-MB-231).