Discovery of Efrotomycin Congeners and Heterologous Expression-Based Insights into the Self-Resistance Mechanism

Chunyan Fang; Qingbo Zhang; Wenjun Zhang; Changsheng Zhang; Yiguang Zhu

doi:10.1021/acs.jnatprod.2c00986

Discovery of Efrotomycin Congeners and Heterologous Expression-Based Insights into the Self-Resistance Mechanism

J Nat Prod. 2022 Dec 23;85(12):2865-2872. doi: 10.1021/acs.jnatprod.2c00986. Epub 2022 Nov 29.

Authors

Chunyan Fang^{1

2}, Qingbo Zhang^{1

2

3

4}, Wenjun Zhang^{1

2

3

4}, Changsheng Zhang^{1

2

3

4}, Yiguang Zhu^{1

2

3

4}

Affiliations

¹ Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, RNAM Center for Marine Microbiology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, 164 West Xingang Road, Guangzhou 510301, China.
² University of Chinese Academy of Sciences, Beijing 100049, China.
³ Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou), Guangzhou 511458, China.
⁴ Sanya Institute of Ocean Eco-Environmental Engineering, Yazhou Scientific Bay, Sanya 572000, China.

PMID: 36445346
DOI: 10.1021/acs.jnatprod.2c00986

Abstract

Four new efrotomycins, A1-A4 (1-4), were isolated from the salt mine-derived Amycolatopsis cihanbeyliensis DSM 45679 and structurally determined. Efrotomycins A3 (3) and A4 (4) feature a tetrahydrofuran ring configured distinctly from known elfamycins. Heterologous expression of the efrotomycin gene cluster (efr BGC) in Streptomyces lividans SBT18 led to efrotomycin B1 (5), the yield of which was improved several fold upon introduction of the transporter gene efrT, a putative self-resistance determinant outside of the efr BGC.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Actinomycetales*
Multigene Family
Pyridones

Substances

efrotomycin
Pyridones