New Lessons for Combinatorial Biosynthesis from Myxobacteria
The biosynthetic mta gene cluster responsible for myxothiazol formation from the fruiting body forming myxobacterium Stigmatella aurantiaca DW4/3-1 was sequenced and analyzed. Myxothiazol, an inhibitor of the electron transport via the bc 1 -complex of the respiratory chain, is biosynthesized by a u...
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Published in | The Journal of biological chemistry Vol. 274; no. 52; pp. 37391 - 37399 |
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Main Authors | , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
American Society for Biochemistry and Molecular Biology
01.12.1999
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Online Access | Get full text |
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Summary: | The biosynthetic mta gene cluster responsible for myxothiazol formation from the fruiting body forming myxobacterium Stigmatella aurantiaca DW4/3-1 was sequenced and analyzed. Myxothiazol, an inhibitor of the electron transport via the bc
1 -complex of the respiratory chain, is biosynthesized by a unique combination of several polyketide synthases (PKS) and nonribosomal
peptide synthetases (NRPS), which are activated by the 4â²-phosphopantetheinyl transferase MtaA. Genomic replacement of a fragment
of mtaB and insertion of a kanamycin resistance gene into mtaA both impaired myxothiazol synthesis. Genes mtaC and mtaD encode the enzymes for bis-thiazol(ine) formation and chain extension on one pure NRPS (MtaC) and on a unique combination
of PKS and NRPS (MtaD). The genes mtaE and mtaF encode PKSs including peptide fragments with homology to methyltransferases. These methyltransferase modules are assumed
to be necessary for the formation of the proposed methoxy- and β-methoxy-acrylate intermediates of myxothiazol biosynthesis.
The last gene of the cluster, mtaG, again resembles a NRPS and provides insight into the mechanism of the formation of the terminal amide of myxothiazol. The
carbon backbone of an amino acid added to the myxothiazol-acid is assumed to be removed via an unprecedented module with homology
to monooxygenases within MtaG. |
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ISSN: | 0021-9258 1083-351X |
DOI: | 10.1074/jbc.274.52.37391 |