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

  • J Nat Prod. 2022 Apr 22;85(4):936-942. doi: 10.1021/acs.jnatprod.1c01075.
Joon Soo An  1 ,  Hyung-Ju Lim  1 ,  Ji Yun Lee  1 ,  Yong-Joon Jang  2 ,  Sang-Jip Nam  3 ,  Sang Kook Lee  1 ,  Dong-Chan Oh  1
Affiliations
  • 1. Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea.
  • 2. Natura Center of Life and Environment, Seoul 08826, Republic of Korea.
  • 3. Department of Chemistry and Nanoscience, Ewha Womans University, Seoul 03760, Republic of Korea.
PMID: 35362983 DOI: 10.1021/acs.jnatprod.1c01075
Abstract

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).