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Polyether Cyclization Cascade Alterations in Response to Monensin Polyketide Synthase Mutations.
Polyether Cyclization Cascade Alterations in Response to Monensin Polyketide Synthase Mutations.
- Source :
-
Chembiochem : a European journal of chemical biology [Chembiochem] 2022 Jan 19; Vol. 23 (2), pp. e202100584. Date of Electronic Publication: 2021 Nov 26. - Publication Year :
- 2022
-
Abstract
- The targeted manipulation of polyketide synthases has in recent years led to numerous new-to-nature polyketides. For type I polyketide synthases the response of post-polyketide synthases (PKS) processing enzymes onto the most frequently polyketide backbone manipulations is so far insufficiently studied. In particular, complex processes such as the polyether cyclisation in the biosynthesis of ionophores such as monensin pose interesting objects of research. We present here a study of the substrate promiscuity of the polyether cyclisation cascade enzymes in monensin biosynthesis in the conversion of redox derivatives of the nascent polyketide chain. LC-HRMS/MS <superscript>2</superscript> -based studies revealed a remarkable flexibility of the post-PKS enzymes. They acted on derivatized polyketide backbones based on the three possible polyketide redox states within two different modules and gave rise to an altered polyether structure. One of these monensin derivatives was isolated and characterized by 2D-NMR spectroscopy, crystallography, and bioactivity studies.<br /> (© 2021 Wiley-VCH GmbH.)
- Subjects :
- Anti-Infective Agents pharmacology
Chromatography, High Pressure Liquid methods
Chromatography, Reverse-Phase
Crystallography, X-Ray
Cyclization
Microbial Sensitivity Tests
Molecular Structure
Monensin analogs & derivatives
Monensin pharmacology
Nuclear Magnetic Resonance, Biomolecular methods
Tandem Mass Spectrometry
Ethers chemistry
Monensin chemistry
Point Mutation
Polyketide Synthases genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1439-7633
- Volume :
- 23
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Chembiochem : a European journal of chemical biology
- Publication Type :
- Academic Journal
- Accession number :
- 34729883
- Full Text :
- https://doi.org/10.1002/cbic.202100584