Over the past two decades, there has been significant interest in engineering microbes to convert low-value and/or abundant resources to produce higher value products like fuels, chemicals, plastics, drugs, etc. Despite extensive efforts, success in engineering microbes to use nutrients they did not naturally evolve to utilize (i.e., non-native substrates) have been not as profound as everyone had hoped. Outcomes so far have indicated that microbes are generally picky-eaters and are reticent to consume unfamiliar substrates. For example, pentose (viz. xylose, arabinose), C1 (CO2, methanol), Cn (cellulose, cellobiose) metabolism in the baker’s yeast, Saccharomyces cerevisiae, is non-optimal, even after extensive engineering efforts compared to that of native C6 sugar nutrients like glucose and galactose Thus, there is significant need in the metabolic engineering and synthetic biology communities to answer the following questions:
- Why has the current engineering paradigm not had greater success?
- How do we engineer microbes to better assimilate substrates they did not naturally evolve to utilize?
- What are the merits of success when evaluating engineering designs?
In this talk, I will present results from our attempt to answer these questions using non-native pentose assimilation by the baker’s yeast S. cerevisiae as a test case.