Catalytic innovation underlies independent recruitment of polyketide synthases in cocaine and hyoscyamine biosynthesis.

ABSTRACT: Tropane alkaloids such as hyoscyamine and cocaine are of importance in medicinal uses. Only recently has the hyoscyamine biosynthetic machinery become complete. However, the cocaine biosynthesis pathway remains only partially elucidated. Here we characterize polyketide synthases required for generating 3-oxo-glutaric acid from malonyl-CoA in cocaine biosynthetic route. Structural analysis shows that these two polyketide synthases adopt distinctly different active site architecture to catalyze the same reaction as pyrrolidine ketide synthase in hyoscyamine biosynthesis, revealing an unusual parallel/convergent evolution of biochemical function in homologous enzymes. Further phylogenetic analysis suggests lineage-specific acquisition of polyketide synthases required for tropane alkaloid bios

SUBMITTER: Tian T 

PROVIDER: S-EPMC9411544 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature