In memory of Prof. Daniel IC Wang： Engineering Y. lipolytica for production of plant-based alternative lipids： technical constrains and perspectives for a sustainable cellular agriculture economy
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2021-04-03
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XU, Peng; In memory of Prof. Daniel IC Wang： Engineering Y. lipolytica for production of plant-based alternative lipids： technical constrains and perspectives for a sustainable cellular agriculture economy; Synthetic Biology Journal, 3 April, 2021; https://doi.org/10.12211/2096-8280.2021-041
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Abstract
Developing cellular agriculture economy is one of the solutions to mitigate resource limitation, reduce greenhouse gas emission, slow down global warming as well as achieve true sustainability. Microbial cell factory has become the critical components to advance biomanufacturing due to the availability of versatile genetic tools, ease to scale-up and high conversion efficiency of low-cost renewable feedstocks. Prof. Daniel IC Wang was one of the trailblazers and founders of biochemical engineering, who built and led the Biotechnology Process Engineering Center (BPEC) at MIT. When I and my colleagues worked as postdoc associates and research scientists in Prof. Stephanopoulos lab, part of our work on engineering oleaginous yeast cell factory was a direct result of the analytical, imaging and cell culture facility at BPEC. Plant-based oil and fats have an overall market value about $200 billion. The recent world has seen a craving for plant oil products, which negatively impacted our environment due to massive-scale deforestation and loss of ecological diversity in tropical regions. We thought oleaginous yeast could be a solution to this problem. Centering around the important genetic targets of the oleaginous species Yarrowia lipolytica, we summarized the essential metabolic engineering strategies to improve the carbon conversion efficiency (yield), lipid titer, lipid production rate (productivity) and cell growth fitness. We further analyzed the technical constraints that limit our ability to build high oil-yielding yeast cell factory, including high throughput strain screening or phenotyping techniques, the incomplete understanding of the lipogenesis and regulatory mechanism, as well as the lack of well-defined biochemical models to guide bioprocess optimization and scale-up. Further we discussed the technical and economic feasibility of converting sugarcane feedstock to high value plant-based lipids with metabolically engineered Y. lipolytica. Our analysis indicates that Y. lipolytica has the great potential to address the current market gap of high value plant-based fats (i.e. cocoa butter equivalent to make chocolate, a potential market of $50 billions). Engineering oleaginous yeast to provide plant-based healthy fats will help us address energy, foods, environment and resource challenges, which will surely move us one step closer to a society of low-carbon footprint and sustainable economy.