Characterization of a new fusicoccane-type diterpene synthase and an associated P450 enzyme.

Beilstein J Org Chem

Institute of Traditional Chinese Medicine & Natural Products, College of Pharmacy / Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research / International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education (MOE) of China, Jinan University, Guangzhou 510632, China.

Published: October 2022

AI Article Synopsis

  • Fusicoccane-type terpenoids are a specialized group of diterpenoids known for their unique 5-8-5 ring structure and various biological activities, but only five synthesizing enzymes are currently identified.
  • A new biosynthetic gene cluster from the strain ATCC 26942 has been discovered, which includes a novel fusicoccane-type diterpene synthase gene, naming it TadA.
  • Experiments show that TadA creates a new compound, talaro-7,13-diene, using a different cyclization process, while another enzyme, TadB, oxidizes this compound into talaro-6,13-dien-5,8-dione.

Article Abstract

Fusicoccane-type terpenoids are a subgroup of diterpenoids featured with a unique 5-8-5 ring system. They are widely distributed in nature and possess a variety of biological activities. Up to date, only five fusicoccane-type diterpene synthases have been identified. Here, we identify a two-gene biosynthetic gene cluster containing a new fusicoccane-type diterpene synthase gene and an associated cytochrome P450 gene from ATCC 26942. Heterologous expression reveals that TadA catalyzes the formation of a new fusicoccane-type diterpene talaro-7,13-diene. DO isotope labeling combined with site-directed mutagenesis indicates that TadA might employ a different C2,6 cyclization strategy from the known fusicoccane-type diterpene synthases, in which a neutral intermediate is firstly formed and then protonated by an environmental proton. In addition, we demonstrate that the associated cytochrome P450 enzyme TadB is able to catalyze multiple oxidation of talaro-7,13-diene to yield talaro-6,13-dien-5,8-dione.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9551204PMC
http://dx.doi.org/10.3762/bjoc.18.144DOI Listing

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