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Solving the Puzzle of One-Carbon Loss in Ripostatin Biosynthesis.
- Source :
- Angewandte Chemie International Edition; 2/13/2017, Vol. 56 Issue 8, p2192-2197, 6p
- Publication Year :
- 2017
-
Abstract
- Ripostatin is a promising antibiotic that inhibits RNA polymerase by binding to a novel binding site. In this study, the characterization of the biosynthetic gene cluster of ripostatin, which is a peculiar polyketide synthase (PKS) hybrid cluster encoding cis- and trans-acyltransferase PKS genes, is reported. Moreover, an unprecedented mechanism for phenyl acetic acid formation and loading as a starter unit was discovered. This phenyl-C2 unit is derived from phenylpyruvate (phenyl-C3) and the mechanism described herein explains the mysterious loss of one carbon atom in ripostatin biosynthesis from the phenyl-C3 precursor. Through in vitro reconstitution of the whole loading process, a pyruvate dehydrogenase like protein complex was revealed that performs thiamine pyrophosphate dependent decarboxylation of phenylpyruvate to form a phenylacetyl- S-acyl carrier protein species, which is supplied to the subsequent biosynthetic assembly line for chain extension to finally yield ripostatin. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 14337851
- Volume :
- 56
- Issue :
- 8
- Database :
- Complementary Index
- Journal :
- Angewandte Chemie International Edition
- Publication Type :
- Academic Journal
- Accession number :
- 121147669
- Full Text :
- https://doi.org/10.1002/anie.201609950