UbiA型萜类环化酶研究进展及其在天然产物合成中的作用

Research progress in UbiA-type terpene cyclases and their roles in natural product biosynthesis

摘要:

UbiA型萜类环化酶是近年来在真菌和细菌中发现的一类新型非经典萜类合成酶，能够催化线性萜类前体通过碳正离子机制发生环化，构建复杂的萜类骨架结构，该类酶的发现显著拓展了天然产物生物合成酶的种类和结构多样性来源。本文系统综述了自2013年首次在烟曲霉(Aspergillus fumigatus)中发现FmaTC以来，共31种UbiA型萜类环化酶的研究进展，涵盖其保守基序特征、系统发育关系、生物合成相关基因簇及产物的结构类型。重点梳理了倍半萜、二萜及二倍半萜等代表性天然产物及其对应的环化酶，探讨了该类酶与细胞色素P450等修饰酶协同作用所产生的化合物，揭示了UbiA家族成员在天然产物多样性形成中的潜在作用。该类酶的发现不仅丰富了萜类生物合成酶库，也为高活性天然产物的生物合成及应用提供了新的研究思路。

Abstract:

UbiA-type terpene cyclases represent a class of non-classical terpenoid synthases recently discovered in fungi and bacteria. These enzymes catalyze the cyclization of linear terpene precursors via a carbocation-mediated mechanism, enabling the construction of complex terpene skeletons. The discovery of these enzymes has significantly expanded the enzymatic toolkit for natural product biosynthesis and broadened the structural diversity of terpenoids. Since the identification of FmaTC in Aspergillus fumigatus in 2013, 31 distinct members of the UbiA family have been characterized. We review the research progress in these enzymes, including their conserved motifs, phylogenetic relationships, biosynthetic gene clusters, and the structural diversity of their products. We highlight representative natural products such as sesquiterpenes, diterpenes, and diheterosesquiterpenes, along with their corresponding cyclases. Additionally, we discuss compounds generated through the synergistic action of these cyclases with modifying enzymes such as cytochrome P450s, shedding light on the potential role of UbiA family members in driving natural product diversity. The discovery of UbiA-type terpene cyclases not only enriches the library of enzymes for the biosynthesis of terpenoids but also gives novel insights into the biosynthesis and application of bioactive natural products.