Enhancing structural diversity of terpenoids by multisubstrate terpene synthases

Min Li; Hui Tao

doi:10.3762/bjoc.20.86

Enhancing structural diversity of terpenoids by multisubstrate terpene synthases

Beilstein J Org Chem. 2024 Apr 30:20:959-972. doi: 10.3762/bjoc.20.86. eCollection 2024.

Authors

Min Li^{1

2

3}, Hui Tao^{1

2

3}

Affiliations

¹ Department of Otolaryngology, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University, Wuhan, Hubei 430071, China.
² Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education, Wuhan University, Wuhan, Hubei 430071, China.
³ TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan, Hubei 430071, China.

Abstract

Terpenoids are one of the largest class of natural products with diverse structures and activities. This enormous diversity is embedded in enzymes called terpene synthases (TSs), which generate diverse terpene skeletons via sophisticated cyclization cascades. In addition to the many highly selective TSs, there are many promiscuous TSs that accept multiple prenyl substrates, or even noncanonical ones, with 6, 7, 8, 11, and 16 carbon atoms, synthesized via chemical approaches, C-methyltransferases, or engineered lepidopteran mevalonate pathways. The substrate promiscuity of TSs not only expands the structural diversity of terpenes but also highlights their potential for the discovery of novel terpenoids via combinatorial biosynthesis. In this review, we focus on the current knowledge on multisubstrate terpene synthases (MSTSs) and highlight their potential applications.

Keywords: noncanonical terpene; substrate promiscuity; synthetic biology; terpene synthase; terpenoid.

Publication types

Review

Grants and funding

This work was financially supported by the National Key R&D Program of China (2023YFA0916200), the Fundamental Research Funds for the Central Universities (2042024kf1039), the Young Elite Scientists Sponsorship Program by CAST (2022QNRC001), the National Natural Science Foundation of China, and TaiKang Center for Life and Medical Sciences.