Advances in mitochondrial compartmentalization for terpenoid synthesis in Saccharomyces cerevisiae.

Mitochondria provide a unique enriched acetyl coenzyme A reservoir and an ideal redox environment, offering an efficient supply for the biosynthesis of terpene precursors and terpene products. This comprehensive review focuses on the engineering of mitochondrial compartmentalization in Saccharomyces cerevisiae to enhance terpene production. We systematically outline the applications from hemiterpenes to tetraterpenes and elaborate on how advanced strategies, such as key enzyme mitochondrial targeting strategy, whole-pathway mitochondrial targeting strategy, dual cytoplasmic-mitochondrial compartmentalization strategy, and multi-organelle synergistic compartmentalization strategy, can effectively improve precursor availability while mitigating metabolic interference and cytotoxic effects. In addition, we critically examine the discussions and long-term challenges associated with these methods. Finally, we highlight the transformative potential of mitochondrial compartmentalization to pioneer future innovations in complex terpene synthesis engineering.