Recent Advances in Multiple Strategies for the Biosynthesis of Sesquiterpenols.

Sesquiterpenols, a class of natural compounds composed of three isoprene units that form a 15-carbon skeleton with hydroxyl (-OH) group, are characterized by their volatility and potent aromatic properties. These compounds exhibit a wide range of biological activities, including antitumor, antibacterial, anti-inflammatory, anti-neurotoxic, antiviral, immunosuppressive, hepatoprotective, and cardiotonic effects. Due to their diverse physiological functionalities, sesquiterpenols serve as critical raw materials in the pharmaceutical, food, and cosmetic industries. In recent years, research on the heterologous synthesis of sesquiterpenol compounds using microbial systems has surged, attracting significant scientific interest. However, challenges such as low yields and high production costs have impeded their industrial-scale application. The rapid development of synthetic biology has introduced innovative methodologies for the microbial production of sesquiterpenol compounds. Herein, we examine the latest synthetic biology strategies and progress in microbial sesquiterpenol production, focusing on adaptive sesquiterpenol synthase screening and expression, synthesis pathway regulation, intracellular compartmentalized expression strategies, and tolerance to terpenoid-related toxicity. Critical challenges and future directions are also discussed to advance research in sesquiterpenol biosynthesis.