Back to Search
Start Over
Solving the Puzzle of One-Carbon Loss in Ripostatin Biosynthesis.
- Source :
-
Angewandte Chemie (International ed. in English) [Angew Chem Int Ed Engl] 2017 Feb 13; Vol. 56 (8), pp. 2192-2197. Date of Electronic Publication: 2017 Jan 18. - 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.<br /> (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Subjects :
- Acyl Carrier Protein genetics
Acyl Carrier Protein metabolism
Acyltransferases genetics
Acyltransferases metabolism
Genes, Bacterial
Multigene Family
Myxococcales genetics
Polyketide Synthases genetics
Polyketide Synthases metabolism
Anti-Bacterial Agents metabolism
Biosynthetic Pathways
Lactones metabolism
Myxococcales metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1521-3773
- Volume :
- 56
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Angewandte Chemie (International ed. in English)
- Publication Type :
- Academic Journal
- Accession number :
- 28098952
- Full Text :
- https://doi.org/10.1002/anie.201609950