B. Silakowski et al., New lessons of combinatorial biosynthesis from myxobacteria - The myxothiazol biosynthetic gene cluster of Stigmatella aurantiaca DW4/3-1, J BIOL CHEM, 274(52), 1999, pp. 37391-37399
The biosynthetic mta gene cluster responsible for myxothiazol formation fro
m the fruiting body forming myxobacterium Stigmatella aurantiaca DW4/3-1 wa
s sequenced and analyzed. Myxothiazol, an inhibitor of the electron transpo
rt via the bc(1)-complex of the respiratory chain, is biosynthesized by a u
nique combination of several polyketide synthases (PKS) and nonribosomal pe
ptide synthetases (NRPS), which are activated by the 4'-phosphopantetheinyl
transferase MtaA. Genomic replacement of a fragment of mtaB and insertion
of a kanamycin resistance gene into mtaA both impaired myxothiazol synthesi
s. Genes mtaC and mtaD encode the enzymes for bis-thiazol(ine) formation an
d chain extension on one pure NRPS (MtaC) and on a unique combination of PK
S and NRPS (MtaD), The genes mtaE and mtaF encode PKSs including peptide fr
agments with homology to methyltransferases, These methyltransferase module
s are assumed to be necessary for the formation of the proposed methoxy- an
d beta-methoxy-acrylate intermediates of myxothiazol biosynthesis. The last
gene of the cluster, mtaG, again resembles a NRPS and provides insight int
o 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 t
o be removed via an unprecedented module with homology to monooxygenases wi
thin MtaG.