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The Mechanism of Dehydrating Bimodules in trans-Acyltransferase Polyketide Biosynthesis: A Showcase Study on Hepatoprotective Hangtaimycin
- Source :
- Angewandte Chemie (International Ed. in English)
- Publication Year :
- 2021
-
Abstract
- A bioassay‐guided fractionation led to the isolation of hangtaimycin (HTM) from Streptomyces spectabilis CCTCC M2017417 and the discovery of its hepatoprotective properties. Structure elucidation by NMR suggested the need for a structural revision. A putative HTM degradation product was also isolated and its structure was confirmed by total synthesis. The biosynthetic gene cluster was identified and resembles a hybrid trans‐AT PKS/NRPS biosynthetic machinery whose first PKS enzyme contains an internal dehydrating bimodule, which is usually found split in other trans‐AT PKSs. The mechanisms of such dehydrating bimodules have often been proposed, but have never been deeply investigated. Here we present in vivo mutations and in vitro enzymatic experiments that give first and detailed mechanistic insights into catalysis by dehydrating bimodules.<br />Hangtaimycin biosynthesis proceeds through a hybrid trans‐AT PKS/NRPS biosynthetic machinery that contains distinctive dehydrating bimodules. Here we present detailed mechanistic insights into catalysis by dehydrating bimodules that are generally involved in the biosynthesis of polyketides with Z double bonds. This work lays the foundations for future structural modifications by protein engineering.
- Subjects :
- chemistry.chemical_classification
Streptomyces spectabilis
Molecular Structure
Stereochemistry
polyketide synthases
Communication
trans-acyltransferase
Total synthesis
General Chemistry
Catalysis
Streptomyces
Communications
chemistry.chemical_compound
Enzyme
Biosynthesis
chemistry
Acyltransferase
Polyketides
Gene cluster
Bimodule
Trans-acting
Natural Products
biosynthesis
Acyltransferases
dehydrating bimodules
Subjects
Details
- ISSN :
- 15213773
- Volume :
- 60
- Issue :
- 35
- Database :
- OpenAIRE
- Journal :
- Angewandte Chemie (International ed. in English)
- Accession number :
- edsair.doi.dedup.....5e80b62a9531bde690d67a974c21406c