Discovery of anti-infective adipostatins through bioactivity-guided isolation and heterologous expression of a type III polyketide synthase.
Bioorg Chem
; 112: 104925, 2021 07.
Article
in English
| MEDLINE | ID: covidwho-1198631
ABSTRACT
Antibiotic resistance and emerging viral pandemics have posed an urgent need for new anti-infective drugs. By screening our microbial extract library against the main protease of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the notorious ESKAPE pathogens, an active fraction was identified and purified, leading to an initial isolation of adipostatins A (1) and B (2). In order to diversify the chemical structures of adipostatins toward enhanced biological activities, a type III polyketide synthase was identified from the native producer, Streptomyces davawensis DSM101723, and was subsequently expressed in an E. coli host, resulting in the isolation of nine additional adipostatins 3-11, including two new analogs (9 and 11). The structures of 1-11 were established by HRMS, NMR, and chemical derivatization, including using a microgram-scale meta-chloroperoxybenzoic acid epoxidation-MS/MS analysis to unambiguously determine the double bond position in the alkyl chain. The present study discovered SARS-CoV-2 main protease inhibitory activity for the class of adipostatins for the first time. Several of the adipostatins isolated also exhibited antimicrobial activity against selected ESKAPE pathogens.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Resorcinols
/
Bacterial Proteins
/
Acyltransferases
/
Anti-Infective Agents
Type of study:
Prognostic study
/
Randomized controlled trials
/
Reviews
Topics:
Traditional medicine
Language:
English
Journal:
Bioorg Chem
Year:
2021
Document Type:
Article
Affiliation country:
J.bioorg.2021.104925
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