The actinomycin biosynthetic gene cluster of Streptomyces chrysomallus: a genetic hall of mirrors for synthesis of a molecule with mirror symmetry

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

Abstract

A gene cluster was identified which contains genes involved in the biosynthesis of actinomycin encompassing 50 kb of contiguous DNA on the chromosome of Streptomyces chrysomallus. It contains 28 genes with biosynthetic functions and is bordered on both sides by IS elements. Unprecedentedly, the cluster consists of two large inverted repeats of 11 and 13 genes, respectively, with four nonribosomal peptide synthetase genes in the middle. Nine genes in each repeat have counterparts in the other, in the same arrangement but in the opposite orientation, suggesting an inverse duplication of one of the arms during the evolution of the gene cluster. All of the genes appear to be organized into operons, each corresponding to a functional section of actinomycin biosynthesis, such as peptide assembly, regulation, resistance, and biosynthesis of the precursor of the actinomycin chromophore 4-methyl-3-hydroxyanthranilic acid (4-MHA). For 4-MHA synthesis, functional analysis revealed genes that encode pathway-specific isoforms of tryptophan dioxygenase, kynurenine formamidase, and hydroxykynureninase, which are distinct from the corresponding enzyme activities of cellular tryptophan catabolism in their regulation and in part in their substrate specificity. Phylogenetic analysis indicates that the pathway-specific tryptophan metabolism in Streptomyces most probably evolved divergently from the normal pathway of tryptophan catabolism to provide an extra or independent supply of building blocks for the synthesis of tryptophan-derived secondary metabolites.

Details

Original languageEnglish
Pages (from-to)2583-2595
Number of pages13
JournalJournal of bacteriology
Volume192
Issue number10
Publication statusPublished - May 2010
Peer-reviewedYes

External IDs

PubMedCentral PMC2863554
Scopus 77952061156
ORCID /0000-0002-2331-2221/work/142242770

Keywords

Keywords

  • Arylformamidase/genetics, Bacterial Proteins/genetics, Chromatography, Thin Layer, Dactinomycin/biosynthesis, Hydrolases/genetics, Molecular Sequence Data, Molecular Structure, Multigene Family/genetics, Mutation, Protein Isoforms/genetics, Sequence Analysis, DNA, Stereoisomerism, Streptomyces/genetics, ortho-Aminobenzoates/metabolism

Library keywords