UC San Diego

Bacterial meroterpenoids are hybrid natural products that partially originate from polyketide synthesis and become highly specialized upon prenylation with terpenoid products. The prenylation event is catalyzed by prenyltransferases (PTases), a class of enzymes that are essential to the biosynthesis of terpenoid compounds such as the napyradiomycins, merochlorins, and marinones. Biochemical assays confirm the prenylation activity of prenyltransferases NapT8 and NapT9 from the napyradiomycin pathway and Mcl23 from the merochlorin pathway in Streptomyces. The study of these PTases was extended to further investigate their structure and specifically focused on studying the substrate promiscuity of NapT8. Results confirmed that NapT8 is highly specific for its prenyl substrate in physiological assay conditions and R58 is speculated to be one of the active site residues responsible for this specificity. Additionally, NapT8 activity has been expanded in the presence of a reducing agent, seemingly producing dechlorinated side products that has not been observed before.

In a parallel study, the activity and specificity of related prenyltransferases CnqP3 and CnqP4 derived from marine Streptomyces sp. CNQ-509 were investigated in the context of a putative neomarinone/marinone gene cluster. Despite confirmation of their prenylation capabilities, results show that CnqP3 and CnqP4 did not produce any observable products with the proposed starter units of the neomarinone pathway or the marinone pathway.