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Discovery of the cryptic function of terpene cyclases as aromatic prenyltransferases

Haibing He, Guangkai Bian, Corey J. Herbst-Gervasoni, Takahiro Mori, Stephen A. Shinsky, Anwei Hou, Xin Mu, Minjian Huang, Shu Cheng, Zixin Deng, David W. Christianson (), Ikuro Abe () and Tiangang Liu ()
Additional contact information
Haibing He: University of Tokyo
Guangkai Bian: Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education and School of Pharmaceutical Sciences, Wuhan University
Corey J. Herbst-Gervasoni: Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania
Takahiro Mori: University of Tokyo
Stephen A. Shinsky: Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania
Anwei Hou: Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education and School of Pharmaceutical Sciences, Wuhan University
Xin Mu: Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education and School of Pharmaceutical Sciences, Wuhan University
Minjian Huang: Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education and School of Pharmaceutical Sciences, Wuhan University
Shu Cheng: Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education and School of Pharmaceutical Sciences, Wuhan University
Zixin Deng: Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education and School of Pharmaceutical Sciences, Wuhan University
David W. Christianson: Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania
Ikuro Abe: University of Tokyo
Tiangang Liu: Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education and School of Pharmaceutical Sciences, Wuhan University

Nature Communications, 2020, vol. 11, issue 1, 1-13

Abstract: Abstract Catalytic versatility is an inherent property of many enzymes. In nature, terpene cyclases comprise the foundation of molecular biodiversity as they generate diverse hydrocarbon scaffolds found in thousands of terpenoid natural products. Here, we report that the catalytic activity of the terpene cyclases AaTPS and FgGS can be switched from cyclase to aromatic prenyltransferase at basic pH to generate prenylindoles. The crystal structures of AaTPS and FgGS provide insights into the catalytic mechanism of this cryptic function. Moreover, aromatic prenyltransferase activity discovered in other terpene cyclases indicates that this cryptic function is broadly conserved among the greater family of terpene cyclases. We suggest that this cryptic function is chemoprotective for the cell by regulating isoprenoid diphosphate concentrations so that they are maintained below toxic thresholds.

Date: 2020
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-17642-2

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DOI: 10.1038/s41467-020-17642-2

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