Engineering Saccharomyces cerevisiae YPH499 for Overproduction of Geranylgeraniol.

Optimization of supply and conversion efficiency of geranylgeranyl diphosphate (GGPP) is important for enhancing geranylgeraniol (GGOH) production in . In this study, first, a strain producing 26.92 ± 1.59 mg/g of dry cell weight squalene was constructed with overexpression of all genes of the mevalonate (MVA) pathway, and an engineered strain producing 597.12 mg/L GGOH at the shake flask level was obtained. Second, through additional expression of - and -, and downregulating expression of , the GGOH titer was increased to 1221.96 mg/L. Then, a NADH HMG-CoA reductase from () was introduced to alleviate the high dependence of the strain upon NADPH, and the GGOH production was further increased to 1271.14 mg/L. Finally, the GGOH titer reached 6.33 g/L after optimizing the fed-batch fermentation method in a 5 L bioreactor, with a 24.9% improvement from the previous report. This study might accelerate the process of developing cell factories for diterpenoid and tetraterpenoid production.