A cryptic type I polyketide synthase (cpk) gene cluster in Streptomyces coelicolor A3(2)

Abstract

The chromosome of Streptomyces coelicolor A3(2), a model organism for the genus Streptomyces, contains a cryptic type I polyketide synthase (PKS) gene cluster which was revealed when the genome was sequenced. The ca. 54-kb cluster contains three large genes, cpkA, cpkB and cpkC, encoding the PKS subunits. In silico analysis showed that the synthase consists of a loading module, five extension modules and a unique reductase as a terminal domain instead of a typical thioesterase. All acyltransferase domains are specific for a malonyl extender, and have a B-type ketoreductase. Tailoring and regulatory genes were also identified within the gene cluster. Surprisingly, some genes show high similarity to primary metabolite genes not commonly identified in any antibiotic biosynthesis cluster. Using western blot analysis with a PKS subunit (CpkC) antibody, CpkC was shown to be expressed in S. coelicolor at transition phase. Disruption of cpkC gave no obvious phenotype.

Taxonomy, Physiology, and Natural Products of Actinobacteria

“…For example, those produced by S. coelicolor include actinorhodin (Act [334]), undecylprodigiosin (Red [335]), calcium-dependent antibiotic (CDA [336]), and methylenomycin (Mmy [337]), the latter of which is carried on a plasmid. However, when the genome sequence of S. coelicolor was published (263), it became apparent that this species' true potential as a producer of natural products had actually been underestimated: over 20 biosynthetic gene clusters for secondary metabolites were identified (338), including one that appears to be for the production of a cryptic polyketide antibiotic (Cpk [339]). It rapidly became apparent that such "concealment" of antibioticproducing capabilities is the norm rather than the exception, with some streptomycetes harboring more than 50 different secondary metabolite gene clusters (340)(341)(342)(343).…”

Genome-wide survey of polyketide synthase and nonribosomal peptide synthetase gene clusters in Streptomyces turgidiscabies NBRC 16081

“…One cluster was composed of STTGS_18_01720, STTGS_18_ 01730 and STTGS_18_ 01740. These three ORFs showed similarities to SCO6273, SCO6274 and SCO6275, respectively (Gottelt et al, 2010;Pawlik et al, 2007). However, the domain organizations of STTGS_ 18_ 01730 (KS/AT/ ACP) and SCO6274 (KS/ AT/ DH/ KR/ ACP-KS/ AT/ DH/ KR/ ACP) were quite different from each other, although those of STTGS_18_01720 and STTGS_18_01740 were identical to those of SCO6273 and SCO6275, respectively.…”

The master regulator PhoP coordinates phosphate and nitrogen metabolism, respiration, cell differentiation and antibiotic biosynthesis: comparison in Streptomyces coelicolor and Streptomyces avermitilis

“…These include, a type III polyketide synthetase gene (SCO7221) involved in germicidin biosynthesis 34 activated following phosphate starvation, although PhoP has a limited effect. The same occurs to several cpk genes, 4,9 involved in biosynthesis of the polyketide coelimycin P1, 35 which includes an oxoacyl acyl carrier protein synthetase. Expression of the cpk cluster for coelimycin P1 biosynthesis is dependent of the phoP gene, 19 although Rodríguez-García et al 4 found that the cpk genes are transiently downregulated by PhoP.…”