Analysis of the Tetronomycin Gene Cluster: Insights into the Biosynthesis of a Polyether Tetronate Antibiotic
- 28 April 2008
- journal article
- research article
- Published by Wiley in ChemBioChem
- Vol. 9 (7), 1136-1145
- https://doi.org/10.1002/cbic.200700715
Abstract
The biosynthetic gene cluster for tetronomycin (TMN), a polyether ionophoric antibiotic that contains four different types of ring, including the distinctive tetronic acid moiety, has been cloned from Streptomyces sp. NRRL11266. The sequenced tmn locus (113 234 bp) contains six modular polyketide synthase (PKS) genes and a further 27 open-reading frames. Based on sequence comparison to related biosynthetic gene clusters, the majority of these can be assigned a plausible role in TMN biosynthesis. The identity of the cluster, and the requirement for a number of individual genes, especially those hypothesised to contribute a glycerate unit to the formation of the tetronate ring, were confirmed by specific gene disruption. However, two large genes that are predicted to encode together a multifunctional PKS of a highly unusual type seem not to be involved in this pathway since deletion of one of them did not alter tetronomycin production. Unlike previously characterised polyether PKS systems, oxidative cyclisation appears to take place on the modular PKS rather than after transfer to a separate carrier protein, while tetronate ring formation and concomitant chain release share common mechanistic features with spirotetronate biosynthesis.Keywords
This publication has 38 references indexed in Scilit:
- Glyceryl‐S‐Acyl Carrier Protein as an Intermediate in the Biosynthesis of Tetronate AntibioticsChemBioChem, 2007
- Elucidation of the Kijanimicin Gene Cluster: Insights into the Biosynthesis of Spirotetronate Antibiotics and NitrosugarsJournal of the American Chemical Society, 2007
- Insights into Polyether Biosynthesis from Analysis of the Nigericin Biosynthetic Gene Cluster in Streptomyces sp. DSM4137Cell Chemical Biology, 2007
- Assembly-Line Enzymology for Polyketide and Nonribosomal Peptide Antibiotics: Logic, Machinery, and MechanismsChemical Reviews, 2006
- Combinatorial biosynthesis of reduced polyketidesNature Reviews Microbiology, 2005
- Mechanisms for incorporation of glycerol-derived precursors into polyketide metabolitesJournal of Industrial Microbiology & Biotechnology, 2005
- Divergent sequence motifs correlated with the substrate specificity of (methyl)malonyl‐CoA:acyl carrier protein transacylase domains in modular polyketide synthasesFEBS Letters, 1995
- RK‐682, a potent inhibitor of tyrosine phosphatase, arrested the mammalian cell cycle progression at G1phaseFEBS Letters, 1995
- Refined Crystal Structure of the Catalytic Domain of Dihydrolipoyl Transacetylase (E2p) from Azotobacter vinelandii at 2·6 Å ResolutionJournal of Molecular Biology, 1993
- Biosynthesis of the polyketide antibiotic ICI139603 in Streptomyces longisporoflavus: assignment of the 13C n.m.r. spectrum by two-dimensional methods, and determination of the origin of the carbon atomsJournal of the Chemical Society, Chemical Communications, 1984