Genome-Based Mining of Carpatamides I-M and Their Candidate Biosynthetic Gene Cluster

Mar Drugs. 2024 Nov 20;22(11):521. doi: 10.3390/md22110521.

Abstract

Chemically investigating the marine-derived Streptomyces parvus 1268 led to the isolation of a new compound of carpatamide I (1). Subsequent genomic analysis identified its candidate biosynthetic gene cluster ctd of approximately 44 kb. In order to obtain more carpatamide derivatives, we conducted the upregulation of Ctd14, which is a positive regulator, and obtained improvement of carpatamide I and four new compounds of carpatamides J-M (2-5). The structures of the aforementioned five new isolates were identified by a combination of ESI-HRMS as well as one-dimensional (1D) and two-dimensional (2D) spectral NMR datasets. Bioassay results showed that compounds 1-5 displayed anti-inflammatory activity and weak cytotoxicity against cell lines of A549, HT-29, and HepG2.

Keywords: carpatamides; genome mining; manumycin; natural products.

MeSH terms

  • A549 Cells
  • Anti-Inflammatory Agents / pharmacology
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • HT29 Cells
  • Hep G2 Cells
  • Humans
  • Multigene Family*
  • Streptomyces* / genetics
  • Streptomyces* / metabolism

Substances

  • Anti-Inflammatory Agents
  • Antineoplastic Agents