Enhancing structural diversity of terpenoids by multisubstrate terpene synthases

Area of Science:

• Biochemistry
• Natural Product Chemistry
• Enzymology

Background:

• Terpenoids represent a vast class of natural products with significant structural and functional diversity.
• Terpene synthases (TSs) are enzymes responsible for generating this diversity through complex cyclization reactions.
• While many TSs are highly selective, some exhibit substrate promiscuity, accepting various prenyl substrates.

Purpose of the Study:

• To review the current understanding of multisubstrate terpene synthases (MSTSs).
• To highlight the potential applications of MSTSs in expanding terpenoid structural diversity.
• To explore the utility of MSTSs in the discovery of novel terpenoids via combinatorial biosynthesis.

Main Methods:

• Focuses on existing literature and research regarding terpene synthases and their substrates.
• Discusses the synthesis of noncanonical substrates (6, 7, 8, 11, and 16 carbons) using chemical methods, C-methyltransferases, and engineered pathways.
• Reviews studies demonstrating the substrate promiscuity of certain terpene synthases.

Main Results:

• Multisubstrate terpene synthases (MSTSs) are capable of utilizing a range of prenyl substrates, including noncanonical ones.
• This substrate promiscuity significantly expands the structural diversity of accessible terpenoids.
• The ability of MSTSs to accept multiple substrates opens avenues for combinatorial biosynthesis.

Conclusions:

• MSTSs are key enzymes for generating diverse terpenoid structures.
• The promiscuity of MSTSs is a valuable asset for discovering novel terpenoids.
• Further research into MSTSs can unlock significant potential in natural product discovery and synthetic biology.