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.

中文翻译：

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通过优化途径和底盘代谢提高酿酒酵母中番茄红素的产量

摘要 番茄红素是一种含有13个双键的四萜类化合物，具有重要的医药和工业应用价值。然而，从天然宿主中提取的原料供应不稳定以及化学合成产品中化学试剂的残留限制了番茄红素的质量。因此，工程微生物被认为是番茄红素生产的替代和有吸引力的途径。为了提高工程酵母合成番茄红素的能力，我们对番茄红素的生物合成途径和底盘代谢进行了优化。结果证实，酿酒酵母CEN.PK2-1C具有较强的萜类化合物前体合成能力，更适合生产番茄红素。与使用诱导型启动子相比，使用控制通路表达的组成型启动子更有效地平衡番茄红素合成和底盘代谢。GGPP 被鉴定为控制速率的代谢物。通过扩大GGPP库和MVA途径，番茄红素产量因此显着增加。通过柠檬酸补料分批发酵，番茄红素的产量最终达到115.64 mg/L，是初始工程酵母的2689倍。这些结果表明，异源途径和底盘代谢的共同优化是强制微生物过度生产天然产物的好策略。番茄红素的产量最终达到115.64 mg/L，是初始工程酵母的2689倍。这些结果表明，异源途径和底盘代谢的共同优化是强制微生物过量生产天然产物的好策略。番茄红素的产量最终达到115.64 mg/L，是初始工程酵母的2689倍。这些结果表明，异源途径和底盘代谢的共同优化是强制微生物过量生产天然产物的好策略。