Kirromycin is produced by Streptomyces collinus Tü 365. This compound is synthesized by a large assembly line of type I polyketide synthases and non-ribosomal peptide synthetases (PKS I/NRPS), encoded by the genes kirAI-kirAVI and kirB. The PKSs KirAI-KirAV have no acyltransferase domains integrated into the PKS modules. This type of PKS is named trans-AT-PKS. The KirAVI belongs to the classical cis-AT-type PKS, where the ATs are part of the PKS protein. In the gene cluster of kirromycin two separate AT-like genes, kirCI and kirCII, were identified. The proteins KirCI and KirCII were characterized by genetic and biochemical approaches. While KirCI is a malonyl-CoA specific AT and loads malonate on the assembly line, the discrete AT KirCII is introducing ethylmalonate into the kirromycin structure. Recently, the substrate preference of KirCII was described (1-3). In vitro assays showed that besides ethylmalonyl-CoA, KirCII accepts other non-malonyl-CoA substrates (e.g. allylmalonyl-CoA or propagylmalonyl-CoA). Feeding of the kirromycin producer strain carrying a Co-A-synthetase led to the production of kirromycin derivatives: allyl- and propagyl-kirromycin and demonstrate that KirCII is also introducing the non-native substrates in an in vivo context. Thus, KirCII represents a promising tool for polyketide diversification.
|Title of host publication||Abstract Book - DTU Sustain Conference 2014|
|Number of pages||1|
|Place of Publication||Kgs. Lyngby|
|Publisher||Technical University of Denmark|
|Publication status||Published - 2014|
|Event||DTU Sustain Conference 2014 - Technical University of Denmark, Lyngby, Denmark|
Duration: 17 Dec 2014 → 17 Dec 2014
|Conference||DTU Sustain Conference 2014|
|Location||Technical University of Denmark|
|Period||17/12/2014 → 17/12/2014|
Musiol-Kroll, E. M., Härtner, T., Kulik, A., Wohlleben, W., Weber, T., & Lee, S. Y. (2014). KirCII- promising tool for polyketide diversification. In Abstract Book - DTU Sustain Conference 2014 Kgs. Lyngby: Technical University of Denmark.