Valhidepsin Lipopeptides from Chromobacterium vaccinii : Structures, Biosynthesis, and Coregulation with FR900359 Production.

Autor: Pistorius D; Global Discovery Chemistry, Novartis Institutes for BioMedical Research, Novartis Pharma AG, Novartis Campus, 4056 Basel, Switzerland., Buntin K; Global Discovery Chemistry, Novartis Institutes for BioMedical Research, Novartis Pharma AG, Novartis Campus, 4056 Basel, Switzerland., Richard E; Global Discovery Chemistry, Novartis Institutes for BioMedical Research, Novartis Pharma AG, Novartis Campus, 4056 Basel, Switzerland., Rust M; Global Discovery Chemistry, Novartis Institutes for BioMedical Research, Novartis Pharma AG, Novartis Campus, 4056 Basel, Switzerland., Bouquet C; Global Discovery Chemistry, Novartis Institutes for BioMedical Research, Novartis Pharma AG, Novartis Campus, 4056 Basel, Switzerland., Wollbrett S; Global Discovery Chemistry, Novartis Institutes for BioMedical Research, Novartis Pharma AG, Novartis Campus, 4056 Basel, Switzerland., Weber E; Global Discovery Chemistry, Novartis Institutes for BioMedical Research, Novartis Pharma AG, Novartis Campus, 4056 Basel, Switzerland., Dietschin D; Global Discovery Chemistry, Novartis Institutes for BioMedical Research, Novartis Pharma AG, Novartis Campus, 4056 Basel, Switzerland., Bruccoleri R; Congenomics, LLC, Glastonbury, Connecticut 06033, United States., Oakeley E; Chemical Biology & Therapeutics, Novartis Institutes for BioMedical Research, Novartis Pharma AG, Novartis Campus, 4056 Basel, Switzerland., Petersen F; Global Discovery Chemistry, Novartis Institutes for BioMedical Research, Novartis Pharma AG, Novartis Campus, 4056 Basel, Switzerland.
Jazyk: angličtina
Zdroj: Journal of natural products [J Nat Prod] 2023 Feb 24; Vol. 86 (2), pp. 246-255. Date of Electronic Publication: 2023 Feb 06.
DOI: 10.1021/acs.jnatprod.2c00825
Abstrakt: Microbial secondary metabolites continue to provide a valuable source of both chemical matter and inspiration for drug discovery in a broad range of therapeutic areas. Beyond this, the corresponding microorganisms represent a sustainable modality for biotechnological production of structurally complex molecules at the quantities required for drug development or even commercial manufacturing. Chromobacterium vaccinii , which has recently been reported as a producer of the pharmacologically highly important G q inhibitor FR900359 (FR), represents such an example. The characterization of an orphan biosynthetic gene cluster (BGC) located directly downstream of the frs BCG led to the discovery of eight new lipopeptides, valhidepsins A-H ( 1 - 8 ), produced by C. vaccinii . Their chemical structures were elucidated through analysis of 1D and 2D NMR data and high-resolution MS/MS fragmentation methods. The valhidepsins did not display significant antibiotic nor cytotoxic activities but showed surfactant properties. The cluster-compound correlation was demonstrated by generation of a knockout mutant, which abolished production of valhidepsins. This knockout mutant yielded a significantly increased isolated yield of FR.
Databáze: MEDLINE
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