Discovery, Biosynthesis, and Heterologous Production of Loonamycin, a Potent Anticancer Indolocarbazole Alkaloid

Org Lett. 2020 Jun 19;22(12):4665-4669. doi: 10.1021/acs.orglett.0c01456. Epub 2020 Jun 2.

Abstract

Genome mining of an indolocarbazole-type gene cluster from a marine-derived Nocardiopsis flavescens NA01583 strain led to the discovery of three new indolocarbazole alkaloids (1-3). Heterologous expression of the intact loo gene cluster in a surrogate host Streptomyces lividans K4-114 led to the successful production of 3. Notably, compound 1 showed potent cytotoxic activities toward eight cancer cell lines with IC50 values ranging from 41 to 283 nM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / biosynthesis*
  • Alkaloids / chemistry
  • Alkaloids / pharmacology*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / metabolism*
  • Antineoplastic Agents / pharmacology*
  • Carbazoles / chemistry*
  • Cell Line, Tumor
  • Drug Design*
  • Humans
  • Inhibitory Concentration 50
  • Streptomyces / metabolism

Substances

  • Alkaloids
  • Antineoplastic Agents
  • Carbazoles