Engineered sugar uptake in yeast cells

The technology focuses on engineered transporter proteins that enhance the uptake of specific monosaccharides like xylose and arabinose into yeast cells, improving their efficiency and selectivity for biofuel and biochemical production.

Background

The efficient conversion of lignocellulosic biomass into biofuels and bio­chemicals is a critical goal in sustainable energy and industrial biotechnology. One of the major challenges in this process is the effective utilization of pentose sugars, such as xylose and arabinose, which are abundant in ligno­cellulosic biomass. Yeast, particularly S. cerevisiae, is a preferred organism for industrial fermentation due to its robustness and ease of genetic manipulation. However, S. cerevisiae lacks an efficient native pathway for xylose and arabinose metabolism, primarily due to the absence of effective transport systems for these sugars.

Existing approaches have focused on optimizing intracellular metabolic pathways to improve xylose and arabinose utilization, but these efforts are often limited by the initial step of sugar transport into the cell. Transporter proteins play a crucial role in this process, and their preferences, regulation, and kinetics significantly impact the overall carbon flux and efficiency of sugar conversion. Despite decades of research, the development of yeast strains with efficient and selective transport systems for pentose sugars remains an outstanding challenge, necessitating innovative solutions to enhance the transport and subsequent metabolism of these sugars in yeast cells.

Technology description

The technology focuses on the development of compositions and methods for transporting specific monosaccharides like xylose and arabinose into yeast cells. Central to this technology is the creation of recombinant transporter proteins that feature specific transporter motif sequences. Some key sequences, which align with amino acid positions 36-41 of the C. intermedia GXS1 protein, are engineered to improve the efficiency and selectivity of sugar transport. The transporter proteins are further refined through mutations at key amino acid residues to fine-tune their transport characteristics. Yeast cells are genetically modified to express these recombinant transporter proteins, thereby enhancing their ability to metabolize these sugars efficiently. This is particularly relevant for applications in biofuel production and biochemical synthesis, where the effective transport of sugars into yeast cells is essential.

What differentiates this technology is its precise engineering of transporter proteins to preferentially uptake xylose or arabinose over other sugars such as glucose. The specific transporter motif sequences significantly influence the transporter's selectivity and efficiency, making these recombinant proteins highly specialized. Additionally, the ability to mutate specific amino acids within these sequences allows for a fine-tuning of transport properties, providing a level of control that is not typically achievable with natural transporter proteins. This specificity and adaptability make the technology highly valuable for industrial processes that rely on the efficient conversion of lignocellulosic biomass into biofuels and biochemicals, addressing a critical bottleneck in the metabolic engineering of yeast cells.

Benefits

  • Enhanced transport efficiency and selectivity of xylose and arabinose over glucose
  • Optimization of sugar transport profiles and rates for improved metabolic engineering
  • Engineered yeast cells can efficiently metabolize specific sugars.
  • Recombinant transporters can be fine-tuned by mutating specific amino acid residues.
  • Facilitates the conversion of lignocellulosic biomass into fuels and chemicals
  • Enhances applications in biofuel production and biochemical synthesis

Commercial applications

  • Biofuel production
  • Biochemical synthesis
  • Industrial fermentation
  • Metabolic engineering

IP link

Issued patent US 9,926,347