Issue 15, 2019

Characterization of MtdV as a chorismate lyase essential to A201A biosynthesis and precursor-directed biosynthesis of new analogs

Abstract

The antimicrobial nucleoside antibiotic A201A is produced by the deep-sea derived Marinactinospora thermotolerans SCSIO 00652. Bioinformatics analysis revealed that mtdV, downstream within the A201A biosynthetic gene cluster, encodes a protein with low homology to a group of chorismate pyruvate-lyases. To explore the role of mtdV in A201A biosynthesis, mtdV was inactivated and HPLC analysis revealed that the resulting ΔmtdV mutant failed to produce A201A; production was partially restored by adding exogenous 4-hydroxybenzoic acid (4HB) to the fermentation. In vitro biochemical assays showed that MtdV catalyzes the conversion of chorismate into 4HB, thereby firmly demonstrating that MtdV is a chorismate lyase involved in A201A biosynthesis. In addition, supplementation of the ΔmtdV mutant with various 4HB analogs enabled production of seven new A201A analogs. Antimicrobial assays showed that the purified A201A analogs 3′-F-A201A and 3′-Cl-A201A were just as active as A201A against the test strains with MIC values of 1–8 μg mL−1.

Graphical abstract: Characterization of MtdV as a chorismate lyase essential to A201A biosynthesis and precursor-directed biosynthesis of new analogs

Supplementary files

Article information

Article type
Paper
Submitted
15 Nov. 2018
Accepted
23 Janv. 2019
First published
29 Janv. 2019

Org. Biomol. Chem., 2019,17, 3760-3764

Characterization of MtdV as a chorismate lyase essential to A201A biosynthesis and precursor-directed biosynthesis of new analogs

Q. Zhu, Y. Song, H. Huang, Q. Li and J. Ju, Org. Biomol. Chem., 2019, 17, 3760 DOI: 10.1039/C8OB02852D

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