報 告 人：Ramon Gonzalez, Department of Chemical& Biomedical Engineering, University of South Florida, Tampa, FL, USA
報告題目：Towards orthogonal metabolism for the biomanufacturing of small organic molecules
報告摘要：Since its inception, the field of metabolic engineering has endeavored to engineer microbial cells by manipulating the canonical “bow-tie” architecture of metabolism. However, even with extensive understanding of heterologous pathways and host metabolism of model microbes, the inherent complexity of the underlying metabolic networks results in problematic crosstalk between product-forming and growth-sustaining functions that compete for the same carbon and energy carriers. The intricate regulation of central metabolism results in additional complexity, impairing the ability to divert carbon flux from central metabolites to molecules of interest, ultimately requiring a significant burden of knowledge that limits the engineering of non-model microbes. These issues pose a number of challenges for the microbial production of small organic molecules at industrially relevant titers, rates, and yields.
Our laboratory has been addressing the above shortcomings by engineering metabolic pathways that are orthogonal to the host metabolism and hence have the potential to operate efficiently, are amenable to different hosts, and can be deployed as both in vitro and in vivo platforms. Our efforts in this area started when we pioneered the engineering of an iterative pathway for the efficient synthesis of longer-chain alcohols and carboxylic acids (Nature, 476:355-359, 2011), which we termed the ？-oxidation reversal (r-BOX). We have further engineered the r-BOX to improve its orthogonality and achieve the synthesis of a host of functionalized small molecules at high carbon and energy efficiency (Nature Biotechnol, 34:556-561, 2016). Building on these successes, we have also engineered new-to-nature pathways for the synthesis of isoprenoids (PNAS, 116:12810-12815, 2019) and polyketides (MS in Review, 2019), as well as the bioconversion of one-carbon substrates (Nature Chem Biol, 15:900-906, 2019). In this talk, I will discuss the challenges and opportunities in the development of orthogonal metabolic platforms for the efficient biomanufacturing of small organic molecules with chemical and pharmaceutical applications.
Dr. Ramon Gonzalez is a Professor and Florida World Class Scholar in the Department of Chemical& Biomedical Engineering at the University of South Florida (USF) where he leads the laboratory for Metabolic Engineering and Biomanufacturing. He is the Editor-in-Chief of the Journal of Industrial Microbiology& Biotechnology. Before joining USF, Dr. Gonzalez was a Professor in the Departments of Chemical & Biomolecular Engineering and Bioengineering at Rice University, the Founding Director of Rice’s Advanced Biomanufacturing Initiative, and from 2012 to 2015 served as Program Director with the Advanced Research Projects Agency-Energy (ARPA-E) of the U.S. Department of Energy.
Dr. Gonzalez’s work has been published in prestigious scientific journals, including Nature, Nature Biotechnology, Nature Chemical Biology, PNAS, and Science. He is the lead inventor in 25 patents and patent applications, co-founded several biotechnology start-ups, and has given more than 100 invited talks.
He is also a member of the editorial boards of Science, Biotechnology Journal, and Metabolic Engineering Communications. Dr. Gonzalez has received numerous recognitions, including elected Fellow of the American Institute for Medical and Biological Engineering, AIChE Division 15c Plenary Lecture, ASM Distinguished Lecturer, SDA/NBB Glycerine Innovation Research Award, and NSF CAREER Award. He obtained a Ph.D. in Chemical Engineering from the University of Chile, an M.S. in Biochemical Engineering from the Pontifical Catholic University of Valparaíso (Chile), and a B.S. in Chemical Engineering from the Central University of Las Villas (Cuba).