Fine-tuning the glycerol biosynthetic pathway in Saccharomyces cerevisiae to optimize the biotechnological production of bio-fuel ethanol and L-glycerol 3-phosphate (L-G3P)

生物乙醇是一种很有前途的化石燃料替代品。在提高生物质向乙醇转化效率的相关途径中，我们希望重点减少主要发酵副产物甘油的产量。除了获得更高的乙醇产量、效价和比生产率外，这种代谢途径修饰还具有降低产品回收成本和减少废物体积的额外优势。减少甘油形成的挑战在于甘油生物合成途径对细胞生长和胁迫耐受性具有几个重要的功能。因此，要完全消除甘油生物合成途径并不是一帆风顺的，我们希望通过微调酶活性来应对这一挑战，以便根据细胞的最低要求调整代谢通量。如果没有税收补贴，生物乙醇生产目前在经济上是不可行的。然而，伴随着高价值副产品的生产，经济效益可以显著提高(S)。3-磷酸甘油L对映体(L-G3P)是一种具有广阔应用前景的高价化学品。本实验室已成功地通过代谢工程在酿酒酵母中积累了这种物质。我们希望进一步提高L-G3P的积累，并通过这样做，评估在生物精炼概念中对酵母生物量增值的可能性。L-G3P是甘油生物合成途径的中间产物。因此，有关甘油积累的研究将协同影响降低甘油的研究。

Bio-ethanol is a promising alternative to fossil fuels. Among the relevant avenues to increase conversion efficiency from biomass to ethanol, we want to focus on reducing the production of the main fermentation by-product glycerol. In addition to achieving higher ethanol yield, titer and specific productivity, such a metabolic pathway modification has the additional advantage to lower the costs for product recovery and reduces waste volumes. The challenge to reduce glycerol formation lies in the fact that the glycerol biosynthetic pathway has several important functions for cell growth and stress tolerance. Therefore, it is not straightforward to completely eliminate the glycerol biosynthetic pathway, and we want to address the challenge by fine-tuning enzyme activities in order to adjust metabolic fluxes according to cells’ minimal requirements. Without tax subsidies, bio-ethanol production is currently not an economically viable process. However, the economic efficiency could be markedly improved by concomitant production of high-value co-product(s). The L-enantiomer of glycerol 3-phosphate (L-G3P), is a high-price chemical with promising applications. Our lab has been successful in accumulating this substance in S. cerevisiae by metabolic engineering. We want to further improve L-G3P accumulation, and by doing so, evaluate the possibility of adding value to yeast biomass in the concept of bio-refining. L-G3P is an intermediate of the glycerol biosynthetic pathway. Hence, studies regarding its accumulation will synergistically affect research on reducing glycerol.