Molecular insights into the catalytic promiscuity of a bacterial diterpene synthase.

ABSTRACT: Diterpene synthase VenA is responsible for assembling venezuelaene A with a unique 5-5-6-7 tetracyclic skeleton from geranylgeranyl pyrophosphate. VenA also demonstrates substrate promiscuity by accepting geranyl pyrophosphate and farnesyl pyrophosphate as alternative substrates. Herein, we report the crystal structures of VenA in both apo form and holo form in complex with a trinuclear magnesium cluster and pyrophosphate group. Functional and structural investigations on the atypical ¹¹⁵DSFVSD¹²⁰ motif of VenA, versus the canonical Asp-rich motif of DDXX(X)D/E, reveal that the absent second Asp of canonical motif is functionally replaced by Ser116 and Gln83, together with bioinformatics analysis identifying a hidden subclass of type I microbial terpene synthases. Fur

SUBMITTER: Li Z 

PROVIDER: S-EPMC10325987 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature