Probing Selectivity and Creating Structural Diversity Through Hybrid Polyketide Synthases.

ABSTRACT: Engineering polyketide synthases (PKS) to produce new metabolites requires an understanding of catalytic points of failure during substrate processing. Growing evidence indicates the thioesterase (TE) domain as a significant bottleneck within engineered PKS systems. We created a series of hybrid PKS modules bearing exchanged TE domains from heterologous pathways and challenged them with both native and non-native polyketide substrates. Reactions pairing wildtype PKS modules with non-native substrates primarily resulted in poor conversions to anticipated macrolactones. Likewise, product formation with native substrates and hybrid PKS modules bearing non-cognate TE domains was severely reduced. In contrast, non-native substrates were converted by most hybrid modules containing a substrate co

SUBMITTER: Koch AA 

PROVIDER: S-EPMC7395861 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature