Abstract:

While several single- and multi-carbon compounds are emerging as cost-effective and potentially carbon-negative feedstocks for biomanufacturing, the development of microbial biocatalysts for their conversion to value-added products remains a challenge. This is in part due to the approaches used for strain engineering, which rely on the canonical architecture of metabolism and entail concurrent engineering of pathways for substrate utilization, central metabolism, and product synthesis. The resulting crosstalk between product-forming and growth-sustaining functions that compete for the same carbon and energy carriers lead to inefficient microbes and bioprocesses that suffer from unreliable scale-up and deployment, expensive downstream processing, and high capital expenses.

We have addressed these shortcomings by pioneering a new approach herein referred to as Orthogonal Biomanufacturing (OrthBioTM). Our OrthBioTM platform relies on the engineering of iterative C1, C2, and C3 elongation pathways (Cn+BioTM) based on acyl-CoA elongation (ACE) reactions that are orthogonal to the host metabolism thus allowing product synthesis independent from cell growth. The ACE reactions include both acyloin condensations between carbonyl compounds, such as aldehydes and ketones, and the C1 moiety formyl-CoA (catalyzed by 2-hydroxyacyl-CoA synthases) as well as non-decarboxylative Claisen condensations between different acyl-CoAs (catalyzed by thiolases). In this talk I will discuss the conceptualization, design and implementation of Cn+BioTM platforms and its deployment for the synthesis of multicarbon products at industrially relevant titers, rates, and yields and with unprecedented scalability across production platforms and scales.

References: Nature 355, 2011; Nat Biotech 556, 2016; Science 6320, 2017; PNAS 12810, 2019; Nat Chem Biol 900, 2019; Nat Metab 1385, 2021; Nat Catal 593, 2020; Nat Comm 3058, 2022; Nat Comm 2682, 2023; Nat Catal 361, 2024.

Speaker’s bio:

Dr. Ramon Gonzalez is the Chief Scientific Officer of MojiaBio and the Director of the Xianghu Laboratory-MojiaBio Synthetic Biology Innovation Center. He is the President of the Society for Industrial Microbiology & Biotechnology (SIMB, founded in 1949) and from 2015 to 2023 served as the Editor-in-Chief of the Journal of Industrial Microbiology & Biotechnology (JIMB), SIMB’s flagship journal. Dr. Gonzalez is an elected Fellow of the American Institute for Medical and Biological Engineering (AIMBE) and the American Association for the Advancement of Science (AAAS). Dr. Gonzalez’s career has spanned the academic, private, and government sectors. Most of his academic work was conducted at Rice University, where he led the laboratory for Metabolic Engineering and Biomanufacturing, rose through the ranks from Assistant Professor to Full Professor, and still serves as Adjunct Professor. While at Rice, he was the founding director of the Advanced Biomanufacturing Initiative and served as Director of the Energy and Environment Initiative. More recently, Dr. Gonzalez was appointed Professor and Florida World Class Scholar in the Department of Chemical, Biological and Materials Engineering at the University of South Florida. In addition to his role as Editor-in-Chief of JIMB, he has served on the Editorial Boards of Science, Biotechnology Journal, Applied and Environmental Microbiology, Applied Biochemistry and Biotechnology, Food Biotechnology. Dr. Gonzalez also served as Program Director with the Advanced Research Projects Agency-Energy (ARPA-E) of the U.S. Department of Energy and with the U.S. National Science Foundation, as well as on the Board of Directors of SIMB.

Dr. Gonzalez has published over 100 papers in prestigious scientific journals, including various Nature portfolio Journals (Nature, Nature Biotechnology, Nature Catalysis, Nature Metabolism, Nature Chemical Biology, Nature Communications), PNAS, and Science and has given more than 100 invited talks at institutions around the world. He is the lead inventor in 25 patents/patent applications and founded/co-founded Glycos Biotechnologies, Creo Ingredients, RBN Bio, and C1Plus Bio. He has advised major industrial bio and Fortune 500 companies and is currently a member of the scientific advisory boards of several companies and research institutions. Dr. Gonzalez has received numerous recognitions, including, Discovery Series Lecture (BioDesign Institute, Arizona State University), Tiangong Forum Lecture (TIB-CAS, China), ‘Inspiring Wisdom’ Distinguished Lecture (SKMML, SJTU, China), AIChE Division 15c Plenary Lecture, ASM Distinguished Lecturer, SDA/NBB Glycerine Innovation Research Award, and NSF CAREER Award. Dr. Gonzalez 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 “Marta Abreu” of Las Villas (Cuba).