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

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.