Improving lycopene production in Saccharomyces cerevisiae through optimizing pathway and chassis metabolism

Abstract

Lycopene, a tetraterpenoid containing 13 double bonds, has important pharmaceutical and industrial application values. However, unstable supply of raw for extracted from natural host and residue of chemical reagents in chemically synthesized products have limited the quality of lycopene. Engineering microorganism is thus regarded as an alternative and attractive route for lycopene production. To improve the ability of engineered yeast to synthesize lycopene, here we have optimized the lycopene biosynthesis pathway and chassis metabolism. The results have verified that S. cerevisiae CEN.PK2-1C was more suitable for lycopene production because of its strong ability of synthesizing precursors of terpenoids. Compared to use inducible promoter, the use of constitutive promoter controlling pathway expression was more efficient for balancing lycopene synthesis and chassis metabolism. GGPP was identified the rate-controlling metabolite. Through expanding GGPP pool and MVA pathway, lycopene production was thus significantly increased. By citric acid fed-batch fermentation, the yield of lycopene finally reached 115.64 mg/L, 2689-folds of initial engineered yeast. These results indicated that co-optimization of heterologous pathway and chassis metabolism is a good strategy for enforcing microbial overproduction of natural products.