Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo, Japan.
Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education and School of Pharmaceutical Sciences, Wuhan University, Wuhan, China.
Nat Commun. 2020 Aug 7;11(1):3958. doi: 10.1038/s41467-020-17642-2.
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.
催化多功能性是许多酶的固有特性。在自然界中，萜烯合酶构成了分子多样性的基础，因为它们生成了在数千种萜类天然产物中发现的各种烃支架。在这里，我们报告说萜烯合酶 AaTPS 和 FgGS 的催化活性可以在碱性 pH 值下从环化酶切换到芳香基烯基转移酶，以生成prenylindoles。AaTPS 和 FgGS 的晶体结构提供了对这种隐匿功能的催化机制的深入了解。此外，在其他萜烯合酶中发现的芳香基烯基转移酶活性表明，这种隐匿功能在更大的萜烯合酶家族中广泛保守。我们认为，这种隐匿功能通过调节异戊二烯二磷酸的浓度来保护细胞免受化学伤害，使其保持在毒性阈值以下。
