Abstract
Plant biomass is a promising carbon source for producing value-added chemicals, including transportation biofuels, polymer precursors, and various additives. Most engineered microbial hosts and a select group of wild-type species can metabolize mixed sugars including oligosaccharides, hexoses, and pentoses that are hydrolyzed from plant biomass. However, most of these microorganisms consume glucose preferentially to non-glucose sugars through mechanisms generally defined as carbon catabolite repression. The current lack of simultaneous mixed-sugar utilization limits achievable titers, yields, and productivities. Therefore, the development of microbial platforms capable of fermenting mixed sugars simultaneously from biomass hydrolysates is essential for economical industry-scale production, particularly for compounds with marginal profits. This review aims to summarize recent discoveries and breakthroughs in the engineering of yeast cell factories for improved mixed-sugar co-utilization based on various metabolic engineering approaches. Emphasis is placed on enhanced non-glucose utilization, discovery of novel sugar transporters free from glucose repression, native xylose-utilizing microbes, consolidated bioprocessing (CBP), improved cellulase secretion, and creation of microbial consortia for improving mixed-sugar utilization. Perspectives on the future development of biorenewables industry are provided in the end.
Highlights
Legitimate concerns regarding the negative environmental impact and unsustainability of the petrochemical industry have resulted in extensive exploration in microbial production of fuels and chemicals (Chu and Majumdar, 2012)
In wild-type yeast, NADPH is mainly regenerated via the oxidative portion of the phosphate pathway (PPP), in which two of the three enzymes involved in converting glucose-6-phosphate (G6P) to D-ribulose-5-phosphate (DRi5P) utilize NADP+ as a cofactor (Figure 1)
S. cerevisiae transformed with xylose reductase (XR), xylose dehydrogenase (XDH), XKS, and TAL1 isolated from S. stipitis grew twice as fast on xylose and produced 70% more ethanol compared to the control strain overexpressing only XR/XDH/XKS (Jin et al, 2005)
Summary
Legitimate concerns regarding the negative environmental impact and unsustainability of the petrochemical industry have resulted in extensive exploration in microbial production of fuels and chemicals (Chu and Majumdar, 2012). In wild-type yeast, NADPH is mainly regenerated via the oxidative portion of the PPP, in which two of the three enzymes involved in converting glucose-6-phosphate (G6P) to D-ribulose-5-phosphate (DRi5P) utilize NADP+ as a cofactor (Figure 1) This conversion is coupled with CO2 formation, inevitably resulting in significant carbon loss and low product yield (Verho et al, 2003). When the ZWF1 gene encoding glucose-6-phosphate dehydrogenase was simultaneously deleted, the K. lactis GAPDH became the major engine replenishing NADPH in recombinant S. cerevisiae, resulting in higher ethanol production rates and yields from xylose compared to those in the control strain. The resulting strains demonstrated improved cell growth rate (0.22 h−1 and 0.17 h−1) and enhanced ethanol production (0.43 g g−1 and 0.29 g g−1) on xylose (Figure 1)
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