Discovery, Biosynthesis, and Heterologous Production of Loonamycin, a Potent Anticancer Indolocarbazole Alkaloid
Cheng Yang, Bo Zhang, Wen Wen Xue, Wu Li, Zi Fei Xu, Jing Shi, Yan Shen, Rui Jiao, Ren Xiang Tan, Hui Ming Ge
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.
Topics & Concepts
Gene clusterHeterologousChemistryHeterologous expressionAlkaloidGeneBiochemistryIC50BiosynthesisStereochemistryIn vitroRecombinant DNAMicrobial Natural Products and BiosynthesisGenomics and Phylogenetic StudiesActinomycetales infections and treatment