460e Understanding and Harnessing the Microbial Fermentation of Glycerol. A New Path for the Production of Biochemicals

Ramon Gonzalez, Departments of Chemical & Biomolecular Engineering and Bioengineering, Rice University, MS-362, P.O. Box 1892, Houston, TX 77251-1892

Glycerol is an abundant, inexpensive, and highly reduced molecule generated as inevitable by-product of biofuels production. The use of glycerol as carbon source in fermentation processes offers the opportunity to produce reduced chemicals at yields higher than those obtained with the use of common sugars. Fully realizing this potential, however, would require the metabolism of glycerol in the absence of external electron acceptors. Unfortunately, fermentative utilization of glycerol is restricted to a small group of microorganisms, most of them not amenable to industrial applications. The synthesis of 1,3-propanediol (1,3-PDO) by these organisms has long been considered the metabolic property that determines their ability to ferment glycerol. For example, E. coli and S. cerevisiae, two microorganisms considered workhorses of modern biotechnology, are unable to synthesize 1,3-PDO and therefore thought to metabolize glycerol only via a respiratory process.

We have recently discovered that E. coli can indeed ferment glycerol in a 1,3-PDO-independent manner. We identified 1,2-propanediol (1,2-PDO) as a fermentation product and established the pathway that mediates its synthesis as well as its role in the metabolism of glycerol. Based on our findings, we proposed a new model for the fermentative utilization of glycerol in which: (1) the production of 1,2-PDO provides a means to consume reducing equivalents generated in the synthesis of cell mass, thus facilitating redox balance, and (2) the conversion of glycerol to ethanol, through a redox-balanced pathway, fulfills energy requirements by generating ATP via substrate-level phosphorylation. Other auxiliary or enabling pathways facilitating this metabolic process were identified along with the culture conditions triggering them, and therefore facilitating glycerol fermentation. We have also shown that this model for the 1,2-PDO-dependent fermentation of glycerol is valid for other microorganisms.

The knowledge base created by the aforementioned studies has been instrumental in the implementation of metabolic engineering strategies to convert glycerol to a variety of products, including lactate, succinate, 1,2-PDO, formate, and ethanol. We will present at the meeting our latest results in the understanding of this new metabolic competency and the metabolic engineering of these microorganisms to produce different chemicals from glycerol.

References:

Dharmadi, Y., Murarka, A., Gonzalez, R. (2006). Biotechnol. Bioeng. 94: 821-829.

Yazdani. S. S., Gonzalez, R. (2007). Curr. Opin. Biotechnol. 18: 213-219.

Murarka. A., Dharmadi, Y., Yazdani, S. S., Gonzalez, R. (2008). App. Environ. Microbiol. 74: 1124-1135.

Gonzalez, R. Murarka. A., Dharmadi, Y., Yazdani, S. S. (2008). Metab. Eng. (In Press).

Yazdani, S. S., Gonzalez, R. (2008). Metab. Eng. (MS in Review).