How Small Molecules are Biomanufactured by Microbes

Abstract:  

Finding a sustainable alternative for today’s petrochemical industry is a major challenge facing chemical engineers and society at large. To be sustainable, routes for converting carbon dioxide into organic compounds for use as both fuels and chemical building blocks must be identified, understood, and engineered. Advances in metabolic engineering, synthetic biology, and other bioengineering disciplines have expanded the scope of what can be produced in a living organism – a field also referred to as biomanufacturing. Here, synthetic biologists apply a general understanding of science (e.g. microbiology, biochemistry) to construct biocatalysts from well-characterized parts (e.g. DNA, protein). Once novel synthetic biological systems (e.g. enzymes for biofuel synthesis) are constructed, they must be engineered to function inside evolving cells without negatively impacting the host’s physiology. These cells are then cultivated in bioreactors at large scale to convert low-cost feedstocks into desirable products that are subsequently purified for final formulation. Biomanufacturing has long been the preferred method of producing complex compounds such as proteins, small molecule natural products (e.g. penicillin), and common fermentation products (e.g. ethanol, lactic acid), and amino acids. The current state of the field is such that virtually any compound could be produced in trace amounts with a dedicated effort, but few novel compounds have been commercialized at large-scale. The future of chemical biomanufacturing will depend on deepening our understanding of microbial metabolism such that cost-effective processes can be robustly developed to leverage wastes and other low-cost feedstocks. In this talk, I will describe pathways for producing chemicals derived from fatty-acids and how my group and others have improved oleochemical production in microbes. The talk will describe the critical regulatory points in native fatty acid metabolism, strategies for deregulating flux, and alternatives that by-pass it altogether. I will highlight the use of heterologous plant enzymes to alter the chain length distribution of products from common long-chain molecules to higher-value medium-chain analogs. I will also highlight strategies that we have used to produce medium-chain fatty alcohols, the highest value compounds in the class, through engineering of thioesterase and thiolase driven pathways. I will comment on efforts we are making to study industrial cultivations at laboratory scale and how these findings lead to further biocatalyst optimization. I will conclude with commentary on the remaining barriers to commercializing these technologies and areas where further research investment could prove fruitful.

Bio:

Brian received his bachelor’s degree in Chemical Engineering from Cornell University and earned his PhD in Chemical Engineering from the University of California-Berkeley. Brian was a postdoctoral fellow at the University of Michigan for two years before starting his career at UW-Madison. Brian is currently the Karen and William Monfre Professor of Chemical and Biological Engineering at UW-Madison with an appointment in the Microbiology Doctoral Training Program. Brian is also serving as the R. Byron Bird Department Chair. Brian’s research group uses systems and synthetic biology approaches to develop biocatalysts for production of small molecules. Brian has advised 23 completed PhDs in his group, 10 postdoctoral fellows, and over 175 undergraduate researchers. His group currently consists of 11 PhD students, 4 postdocs, and 10 undergraduates. Brian has served on the Board of Directors for the Society of Industrial Microbiology and Biotechnology, the ACS BIOT Division, and the International Metabolic Engineering Society. Brian’s research has been recognized with awards from 3M, the Alexander von Humboldt Foundation (Bessel Research award), NSF (CAREER), DOE (Early Career), the Air Force Office of Scientific Research (AFOSR-YIP), Biotechnology and Bioengineering (Daniel IC Wang Award), the Society of Industrial Microbiology and Biotechnology, the American Chemical Society BIOT Division (2018 YI Award), and Purdue University (Mellichamp lectureship). Brian also received the Benjamin Smith Reynolds teaching award from the UW-Madison College of Engineering for his efforts to introduce undergraduates to biotechnology.