- Post Doctoral
MIT Unit Affiliation:
- Biological Engineering
Post Doc Sponsor / Advisor:
Date PhD Completed:
Top 3 Areas of Expertise:
Expected End Date of Post Doctoral Position:
At the MIT-Broad Foundry, accelerating the design-build-test-learn cycle in S. cerevisiae through automating massively parallel pathway synthesis and applying response surface methodology.
At the MIT-Broad Foundry, forward design and modeling of yeast genetic parts with the goal of genome scale design.
At the University of Texas, developed and demonstrated molecular transporter engineering as a tool for metabolic engineering.
Molecular transporters transit small molecules across the cellular membrane and in doing so perform the first true step of any metabolic pathway. Yet, in the context of pathway engineering, molecular transport is largely underexplored and tools for modifying it are underdeveloped. However, in all in vivo contexts, the maximal constraint of metabolic throughput is the rate of molecular transport across the cellular membrane.
This transport limitation is particularly evident when attempting to convert lignocellulosic biomass hydrolysates to value-added compounds using Saccharomyces cerevisiae. S. cerevisiae consumes glucose efficiently, and is genetically tractable, enabling synthesis of many molecules of interest. Yet, it does not consume xylose, the second most abundant sugar in lignocellulosic biomass, comprising up to 30% of the total carbon in these mixtures.
After decades of internal pathway engineering, xylose consumption by recombinant S. cerevisiae remains limited by xylose transport. Here, I present a systematic protein engineering approach to alleviate the transport bottleneck. Through bioprospecting aided by genome databases, promising heterologous xylose transporters were discovered. By implementing directed evolution, important amino acid motifs were identified in these transporters that increase xylose transport efficiency. Targeted saturation mutagenesis and rational combination of mutations within these motifs produced transporters that transport xylose but do not transport glucose, a phenotype not observed for yeasts in nature and ideal for lignocellulosic biomass fermentation.
Through this work, I demonstrate the importance of transport in metabolic pathways and the utility of protein engineering in accomplishing metabolic engineering goals. Therefore, I establish transporter engineering as a tool for metabolic engineering.
Top 5 Awards and honors (name of award, date received):
5 Recent Papers:
Young, E. M. et al. (2014), "Rewiring yeast sugar transporter preference through modifying a conserved protein motif,” Proceedings of the National Academy of Sciences of the United States of America. 111(1): 131-6. http://www.pnas.org/content/111/1/131.short
Young, E. M., et al. (2012), “A molecular transporter engineering approach to improving xylose catabolism in Saccharomyces cerevisiae," Metabolic Engineering. 14(4): 401-11. http://www.sciencedirect.com/science/article/pii/S1096717612000298
Young, E. M., et al. (2011), "Functional survey for heterologous sugar transport proteins, using Saccharomyces cerevisiae as a host," Applied and Environmental Microbiology, 77(10): 3311-9. http://aem.asm.org/content/77/10/3311.short
Young, E. M., et al. (2010), "Optimizing pentose utilization in yeast: the need for novel tools and approaches," Biotechnology for Biofuels, 3(24). http://www.biotechnologyforbiofuels.com/content/3/1/24
Young, E. M. and H. Alper. (2010), "Synthetic biology: Tools to design, build, and optimize cellular processes," Journal of Biomedicine and Biotechnology, 130781. http://www.hindawi.com/journals/bmri/2010/130781/