8ylz
From Proteopedia
Structure of a cis-Geranylfarnesyl Diphosphate Synthase from Streptomyces clavuligerus
Structural highlights
FunctionD5SL65_STRCL Catalyzes the condensation of isopentenyl diphosphate (IPP) with allylic pyrophosphates generating different type of terpenoids.[HAMAP-Rule:MF_01139] Publication Abstract from PubMedcis-Prenyltransferases (cis-PTs) catalyze the sequential head-to-tail condensation of isopentenyl diphosphate (IPP) to allylic diphosphates, producing mixed E-Z prenyl diphosphates of varying lengths; yet, the specific enzymes synthesizing cis-C25 prenyl diphosphates have not been identified. In this study, we present the discovery and characterization of a cis-geranylfarnesyl diphosphate synthase (ScGFPPS) from Streptomyces clavuligerus. This enzyme demonstrates high catalytic proficiency in generating six distinct cis-polyisoprenoids, including three C25 and three C20 variants. We further determine the crystal structure of ScGFPPS. Additionally, we unveil the crystal structure of nerylneryl diphosphate synthase (NNPS), known for synthesizing an all-cis-C20 polyisoprenoid. Comparative structural analysis of ScGFPPS and NNPS has identified key differences that influence product specificity. Through site-directed mutagenesis, we have identified eight single mutations that significantly refine ScGFPPS's selectivity for cis-polyisoprenoids. Our findings not only expand the functional spectrum of cis-PTs but also provide a structural comparison strategy in cis-PTs engineering. Discovery, Structure, and Engineering of a cis-Geranylfarnesyl Diphosphate Synthase.,Li FR, Wang Q, Pan X, Xu HM, Dong LB Angew Chem Int Ed Engl. 2024 Apr 23:e202401669. doi: 10.1002/anie.202401669. PMID:38651244[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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