| Structural highlights
Function
CPT2_SOLLC Uses dimethylallyl diphosphate and isopentenyl diphosphate to catalyze the cis-prenyl chain elongation and produce the 20 carbon product nerylneryl diphosphate.[1] [2] [3]
Publication Abstract from PubMed
cis-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[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Akhtar TA, Matsuba Y, Schauvinhold I, Yu G, Lees HA, Klein SE, Pichersky E. The tomato cis-prenyltransferase gene family. Plant J. 2013 Feb;73(4):640-52. doi: 10.1111/tpj.12063. Epub 2012 Dec 31. PMID:23134568 doi:http://dx.doi.org/10.1111/tpj.12063
- ↑ Matsuba Y, Nguyen TT, Wiegert K, Falara V, Gonzales-Vigil E, Leong B, Schafer P, Kudrna D, Wing RA, Bolger AM, Usadel B, Tissier A, Fernie AR, Barry CS, Pichersky E. Evolution of a complex locus for terpene biosynthesis in solanum. Plant Cell. 2013 Jun;25(6):2022-36. doi: 10.1105/tpc.113.111013. Epub 2013 Jun, 11. PMID:23757397 doi:http://dx.doi.org/10.1105/tpc.113.111013
- ↑ Matsuba Y, Zi J, Jones AD, Peters RJ, Pichersky E. Biosynthesis of the diterpenoid lycosantalonol via nerylneryl diphosphate in Solanum lycopersicum. PLoS One. 2015 Mar 18;10(3):e0119302. PMID:25786135 doi:10.1371/journal.pone.0119302
- ↑ Li FR, Wang Q, Pan X, Xu HM, Dong LB. Discovery, Structure, and Engineering of a cis-Geranylfarnesyl Diphosphate Synthase. Angew Chem Int Ed Engl. 2024 Apr 23:e202401669. PMID:38651244 doi:10.1002/anie.202401669
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