RESUMO
A draft genome sequence of Cystobacter violaceus strain Cb vi76, which produces the eukaryotic protein synthesis inhibitor gephyronic acid, has been obtained. The genome contains numerous predicted secondary metabolite clusters, including the gephyronic acid biosynthetic pathway. This genome will contribute to the investigation of secondary metabolism in other Cystobacter strains.
RESUMO
Gephyronic acid, a cytostatic polyketide produced by the myxobacterium Cystobacter violaceus Cb vi76, exhibits potent and selective eukaryotic protein synthesis inhibition. Next-generation sequencing of the C. violaceus genome revealed five type I polyketide synthases and post-PKS tailoring enzymes including an O-methyltransferase and a cytochrome P450 monooxygenase. Seven methyltransferase (MT) domains embedded within the PKS subunits were found to install the methyl branches throughout the gephyronic acid skeleton. A rare loading domain from the GNAT superfamily also contains an embedded MT domain that catalyzes the in situ production of an isobutyryl starter unit. Phylogenetic analysis identified new motifs that distinguish MT domains located in PKS pathways with in cis acyltransferase (AT) domains from MT domains located in PKS pathways with trans AT enzymes. The identification of the gene cluster sets the stage for the generation of a heterologous expression system, which will allow further investigation of selective eukaryotic protein synthesis inhibitors through the generation of gephyronic acid analogues.