Collaborative Research: SusChEM: Engineering the thermotolerant yeast Kluyveromyces marxianus for the synthesis of biobased chemicals

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This project seeks to develop the thermotolerant yeast Kluyveromyces marxianus as a platform microorganism for industrial bioprocessing. A critical area of the US industrial biotechnology sector is the conversion of biomass and other renewable feedstocks to high value and commodity chemicals. K. marxianus can grow at high temperature and low pH, and on a wide range of different sugars, important traits for economic bioprocesses. The project will develop new genetic engineering tools for this yeast and apply these tools to engineer the bio-production of two important classes of chemicals that are traditionally produced from petroleum feedstocks. The project will also contribute to the training of graduate and undergraduate students, as well as the development of new educational outreach programs for high school and community college students from diverse backgrounds.The overall goal is to establish K. marxianus as a platform host for the production of a broad range of biobased chemicals. Critical to advancing K. marxianus is the development of new synthetic biology tools that can rapidly create strains with multiple genome edits and that can accurately control transcription of native and heterologous genes. This project addresses these challenges by (1) developing new enabling tools and methods for rapid strain development and genome engineering in this yeast species, and (2) applying the tools for metabolic engineering of pathways leading to commercially significant native (acetate esters) and non-native (polyketide) products. Phenylethyl and isoamyl acetate are valuable fragrance/flavor compounds and are used as industrial solvents. Polyketides have significant value as pharmaceuticals, including as antibiotic, anticancer, and cholesterol-lowering drugs. The rationale behind this project is that K. marxianus is a highly promising microbial host for non-aseptic (and aseptic) bioprocesses that can convert a range of different sugars into high-value and industrially-relevant chemicals and proteins. This research is transformational because it develops new synthetic biology tools and metabolic engineering approaches to harness and enhance the native traits of K. marxianus, enabling new bioprocesses for the conversion of renewable feedstocks to valuable products.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.