Elucidation of novel FPP-methyltransferase-terpene synthase gene clusters in Proteobacteria

• Applicant: Professorin Dr. Birgit Piechulla
• Subject Area: Metabolism, Biochemistry and Genetics of Microorganisms ; Biochemistry
• Term: from 2017 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 390586930

The classical biosynthesis of terpenoids is based on the usage of C10-GPP, C15-FPP or C20-GGPP as substrates, but a paradigm change has to be considered. A coupling of C-methylation and cyclization by the FPP methyltransferase with a non-classical terpene synthase represents an unprecedented reaction mechanism which was recently shown for the unique biosynthesis of sodorifen in Serratia plymuthica 4Rx13. It illustrates an alternative avenue to enlarge terpene diversity due to the utilization of a C16 substrate. Substrate specificity of the succeeding sodorifen synthase for the non-canonical, monocyclic pre-sodorifen pyrosphosphate implies the coevolution of both enzymes. Preliminary additional evidence of this coevolution is also found in Pseudomonas chlororaphis O6 which produces the novel bis-homoterpene chlororaphen. So far, C-methylations and cyclizations of prenyl pyrophosphates have been exclusively found in bacteria scrutinizing the origin of respective biosynthetic pathways. We hypothesize that in proteobacteria rather than in actinobacteria (e.g. Streptomyces species) C-methylation and cyclization of FPP was established for the biosynthesis of novel terpenoids. Here we will verify whether the biosynthesis the of C17 compound chlororaphen depends on two preceding methyltransferase reactions which are followed by a terpene synthase reaction. Moreover, we will test the hypothesis whether FPP methyltransferases were (exclusively/dominantly) manifested in proteobacteria during evolution.

• DFG Programme: Research Grants