Genome Mining of Novel Rubiginones from Streptomyces Sp. CB02414 and Characterization of the Post-PKS Modification Steps in Rubiginone Biosynthesis

Overview

Journal Microb Cell Fact

Publisher Biomed Central

Specialties Biotechnology
Microbiology

Date 2021 Oct 3

PMID 34600534

Citations 1

Authors

Jingyan Zhang

Ying Sun

Yeji Wang

Xin Chen

Lu Xue

Jingjing Zhang

Xiangcheng Zhu

Yanwen Duan

Xiaohui Yan

Affiliations

Soon will be listed here.

Abstract

Background: Rubiginones belong to the angucycline family of aromatic polyketides, and they have been shown to potentiate the vincristine (VCR)-induced cytotoxicity against VCR-resistant cancer cell lines. However, the biosynthetic gene clusters (BGCs) and biosynthetic pathways for rubiginones have not been reported yet.

Results: In this study, based on bioinformatics analysis of the genome of Streptomyces sp. CB02414, we predicted the functions of the two type II polyketide synthases (PKSs) BGCs. The rub gene cluster was predicted to encode metabolites of the angucycline family. Scale-up fermentation of the CB02414 wild-type strain led to the discovery of eight rubiginones, including five new ones (rubiginones J, K, L, M, and N). Rubiginone J was proposed to be the final product of the rub gene cluster, which features extensive oxidation on the A-ring of the angucycline skeleton. Based on the production profiles of the CB02414 wild-type and the mutant strains, we proposed a biosynthetic pathway for the rubiginones in CB02414.

Conclusions: A genome mining strategy enabled the efficient discovery of new rubiginones from Streptomyces sp. CB02414. Based on the isolated biosynthetic intermediates, a plausible biosynthetic pathway for the rubiginones was proposed. Our research lays the foundation for further studies on the mechanism of the cytochrome P450-catalyzed oxidation of angucyclines and for the generation of novel angucyclines using combinatorial biosynthesis strategies.

Citing Articles

Genomes and secondary metabolomes of spp. isolated from ssp. .

Malfent F, Zehl M, Kirkegaard R, Oberhofer M, Zotchev S Front Microbiol. 2024; 15:1408479.

PMID: 38946903 PMC: 11212599. DOI: 10.3389/fmicb.2024.1408479.

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