Expanding the structural diversity of terpenes by synthetic biology approaches

Rong Chen; Ming Wang; Jay D Keasling; Tianyuan Hu; Xiaopu Yin

doi:10.1016/j.tibtech.2023.12.006

Expanding the structural diversity of terpenes by synthetic biology approaches

Trends Biotechnol. 2024 Jan 16:S0167-7799(23)00345-1. doi: 10.1016/j.tibtech.2023.12.006. Online ahead of print.

Authors

Rong Chen¹, Ming Wang², Jay D Keasling³, Tianyuan Hu², Xiaopu Yin⁴

Affiliations

¹ Key Laboratory of Elemene Class Anti-Cancer Chinese Medicine of Zhejiang Province, School of Pharmacy, School of Public Health, Hangzhou Normal University, Hangzhou 310000, China; Joint BioEnergy Institute, Emeryville, CA 94608, USA. Electronic address: rongchen1984@hznu.edu.cn.
² Key Laboratory of Elemene Class Anti-Cancer Chinese Medicine of Zhejiang Province, School of Pharmacy, School of Public Health, Hangzhou Normal University, Hangzhou 310000, China.
³ Joint BioEnergy Institute, Emeryville, CA 94608, USA; California Institute for Quantitative Biosciences (QB3), University of California, Berkeley, CA 94720, USA; Department of Chemical and Biomolecular Engineering, University of California, Berkeley, CA 94720, USA; Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA; Department of Bioengineering, University of California, Berkeley, CA 94720, USA; Center for Synthetic Biochemistry, Institute for Synthetic Biology, Shenzhen Institutes of Advanced Technologies, Shenzhen 518055, China; Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Lyngby, Denmark.
⁴ Key Laboratory of Elemene Class Anti-Cancer Chinese Medicine of Zhejiang Province, School of Pharmacy, School of Public Health, Hangzhou Normal University, Hangzhou 310000, China. Electronic address: yinxp@hznu.edu.cn.

PMID: 38233232
DOI: 10.1016/j.tibtech.2023.12.006

Abstract

Terpenoids display chemical and structural diversities as well as important biological activities. Despite their extreme variability, the range of these structures is limited by the scope of natural products that canonically derive from interconvertible five-carbon (C5) isoprene units. New approaches have recently been developed to expand their structural diversity. This review systematically explores the combinatorial biosynthesis of noncanonical building blocks via the coexpression of the canonical mevalonate (MVA) pathway and C-methyltransferases (C-MTs), or by using the lepidopteran mevalonate (LMVA) pathway. Unnatural terpenoids can be created from farnesyl diphosphate (FPP) analogs by chemobiological synthesis and terpene cyclopropanation by artificial metalloenzymes (ArMs). Advanced technologies to accelerate terpene biosynthesis are discussed. This review provides a valuable reference for increasing the diversity of valuable terpenoids and their derivatives, as well as for expanding their potential applications.

Keywords: C-methyltransferase; artificial metalloenzyme; noncanonical terpene; synthetic biology.

Publication types

Review