The Chemical Engineering Department is hosting a special graduate seminar on Fuels, chemicals, and opiates: Engineering diverse microbes for production of natural and new-to-nature bioproducts
Abstract:
Microbial synthesis, in which laboratory microorganisms are engineered to produce sustainable high-value metabolites, overcomes many challenges facing petroleum refining, crop-based manufacturing and total synthesis. This talk highlights recent efforts in the development of three prospective microbial bioprocesses spanning biofuels, platform chemicals, and plant pharmaceuticals.
I will first recap our work in engineering anaerobic bacteria for sustainable production of biobutanol, a high-energy biofuel. I will also outline our progress towards biobased production of cis,cis-muconic acid (CCM) and adipic acid, a precursor to nylon 6,6. We screened 122 strains of yeast from public culture repositories and identified Pichia occidentalis as a robust non-conventional host with tremendous tolerance to organic acids. Domesticating P. occidentalis and cultivating our engineered strain in a fed-batch process enabled CCM production at a yield and productivity that surpasses metrics achieved to date using common brewer’s yeast. Finally, I will describe the construction of a yeast platform for efficient production of tetrahydroisoquinoline alkaloids, a diverse class of more than 3,000 natural products. Controlled cultivation of our host in a fed-batch process yielded near-commercial titers of opiates, a 100,000-fold improvement over previous efforts. We further showcased the biosynthetic potential of our platform by synthesizing an array of chemical scaffolds that have not been observed in nature. A microbial source of plant pharmaceuticals will enable a more sustainable, scalable, and reliable supply of these essential medicines, as well as the opportunity to synthesize new analogues for drug discovery.