The Kavaratamides: Discovery of Linear Lipodepsipeptides from the Marine Cyanobacterium Moorena bouillonii Using a Comparative Chemogeographic Analysis

  • J Nat Prod. 2024 Jun 28;87(6):1601-1610. doi: 10.1021/acs.jnatprod.4c00242.
Byeol Ryu  1 ,  Evgenia Glukhov  1 ,  Thaiz R Teixeira  2 ,  Conor R Caffrey  2 ,  Saranya Madiyan  3 ,  Valsamma Joseph  3 ,  Nicole E Avalon  1 ,  Christopher A Leber  1 ,  C Benjamin Naman  1  4 ,  William H Gerwick  1  5
Affiliations
  • 1. Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California San Diego, 9500 Gilman Drive, La Jolla, California 92093, United States.
  • 2. Center for Discovery and Innovation in Parasitic Diseases, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, 9500 Gilman Drive, La Jolla, California 92093, United States.
  • 3. National Centre for Aquatic Animal Health, Cochin University of Science and Technology, Kochi, Kerala 682016, India.
  • 4. Department of Science and Conservation, San Diego Botanic Garden, 300 Quail Gardens Drive, Encinitas, California 92024, United States.
  • 5. Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, 9500 Gilman Drive, La Jolla, California 92093, United States.
PMID: 38832890 DOI: 10.1021/acs.jnatprod.4c00242
Abstract

Kavaratamide A (1), a new linear lipodepsipeptide possessing an unusual isopropyl-O-methylpyrrolinone moiety, was discovered from the tropical marine filamentous cyanobacterium Moorena bouillonii collected from Kavaratti, India. A comparative chemogeographic analysis of M. bouillonii collected from six different geographical regions led to the prioritized isolation of this metabolite from India as distinctive among our data sets. AI-based structure annotation tools, including SMART 2.1 and DeepSAT, accelerated the structure elucidation by providing useful structural clues, and the full planar structure was elucidated based on comprehensive HRMS, MS/MS fragmentation, and NMR data interpretation. Subsequently, the absolute configuration of 1 was determined using advanced Marfey's analysis, modified Mosher's ester derivatization, and chiral-phase HPLC. The structures of kavaratamides B (2) and C (3) are proposed based on a detailed analysis of their MS/MS fragmentations. The biological activity of kavaratamide A was also investigated and found to show moderate cytotoxicity to the D283-medullablastoma cell line.