Recent Advances in Multiple Strategies for the Synthesis of Terpenes by Engineered Yeast

Terpenes are an important class of natural secondary metabolites with a wide range of applications in food, pharmaceuticals, and biofuels. Currently, the traditional production methods of terpenes almost depend on plant extraction and chemical conversion. The plant extraction method consumes a lot of natural resources and makes it difficult to separate the target compound from the extractives, while the chemical conversion method has a complex synthesis route and leads to severe environmental pollution. Compared to plant extraction and chemical conversion methods, the microbial synthesis method has the advantages of preferable sustainability, low production cost and environmental friendliness, and is a potential way to achieve efficient terpenes production in the future. Yeast is a conventional platform for bio-chemical production and is also engineered to synthesize terpenes due to their abundant intracellular acetyl-CoA, high metabolic flux of the MVA pathway, high local concentrations of substrates and enzymes, and fewer by-products. At present, a variety of terpenes including alpha-farnesene, squalene, limonene, beta-carotene have been successfully synthesized by the engineered yeast via the application of multiple strategies. This work summarized the progress of research on these strategies conducted in the synthesis of terpenes from several aspects, including the adaptive screening and expression of terpene synthases, the regulation of synthesis pathways, and the application of intracellular compartmentalized expression strategy. The perspectives and challenges were also discussed, from which it was hoped that some useful views for future research on the synthesis of terpenes in yeast would be provided.