Discovery and Biosynthesis of Atrovimycin, an Antitubercular and Antifungal Cyclodepsipeptide Featuring Vicinal-dihydroxylated Cinnamic Acyl Chain

Qing Liu; Zhiyong Liu; Changli Sun; Mingwei Shao; Junying Ma; Xiaoyi Wei; Tianyu Zhang; Wenjun Li; Jianhua Ju

doi:10.1021/acs.orglett.9b00618

Discovery and Biosynthesis of Atrovimycin, an Antitubercular and Antifungal Cyclodepsipeptide Featuring Vicinal-dihydroxylated Cinnamic Acyl Chain

Org Lett. 2019 Apr 19;21(8):2634-2638. doi: 10.1021/acs.orglett.9b00618. Epub 2019 Apr 8.

Authors

Qing Liu^{1

2}, Zhiyong Liu³, Changli Sun², Mingwei Shao², Junying Ma², Xiaoyi Wei⁴, Tianyu Zhang^{3

5}, Wenjun Li¹, Jianhua Ju^{2

5}

Affiliations

¹ State Key Laboratory of Biocontrol and Guangdong Provincial Key Laboratory of Plant Resources, School of Life Sciences , Sun Yat-Sen University , Guangzhou 510275 , China.
² CAS 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 , Guangzhou 510301 , China.
³ State Key Laboratory of Respiratory Disease, Guangzhou Regenerative Medicine and Health Guangdong Laboratory (GRMH-GDL) , Guangzhou Institutes of Biomedicine and Health (GIBH), Chinese Academy of Sciences (CAS) , Guangzhou 510530 , China.
⁴ Key Laboratory of Plant Resources Conservation and Sustainable Utilization , South China Botanical Garden, Chinese Academy of Sciences , Guangzhou 510650 , China.
⁵ University of Chinese Academy of Sciences , Beijing 110039 , China.

PMID: 30958008
DOI: 10.1021/acs.orglett.9b00618

Abstract

Atrovimycin (1), a cyclodepsipeptide containing a unique vicinal-hydroxylated cinnamic acyl chain, was isolated and elucidated from Streptomyces atrovirens LQ13. The biosynthetic pathway of 1 was achieved, revealing cytochrome P450 (Avm43) and epoxide hydrolase (Avm29) enzymes constructing the vicinal-dihydroxy substitution, as well as a tailoring P450 (Avm28) enzyme catalyzing β-hydroxylation of the l-Phe moiety. Atrovimycin shows in vitro antifungal activity and antitubercular activity against Mycobacterium tuberculosis H37Rv both in vitro (with MIC of 2.5 μg/mL) and in vivo.

Publication types

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

MeSH terms

Antifungal Agents / chemistry
Antifungal Agents / metabolism*
Antitubercular Agents / metabolism*
Antitubercular Agents / pharmacology
Biocatalysis
Biosynthetic Pathways
Cytochrome P-450 Enzyme System / metabolism
Depsipeptides / biosynthesis*
Depsipeptides / chemistry
Epoxide Hydrolases / metabolism
Hydroxylation
Mycobacterium tuberculosis / drug effects
Streptomyces / metabolism
Structure-Activity Relationship

Substances

Antifungal Agents
Antitubercular Agents
Depsipeptides
atrovimycin
Cytochrome P-450 Enzyme System
Epoxide Hydrolases