Presentation Information
[2BRBP-03]C1-based biomanufacturing using formyl-CoA elongation (FORCE) pathways
○Ramon Gonzalez Gonzalez1 (1. Mojia Biotech and Xianghu Laboratory, Singapore)
Keywords:
formyl-CoA elongation
While one-carbon (C1) 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 an iterative C1 elongation pathway (C1+BioTM) based on formyl-CoA elongation (FORCE) reactions that are orthogonal to the host metabolism thus allowing product synthesis independent from cell growth. The FORCE reactions, catalyzed by 2-hydroxyacyl-CoA synthases (HACS), are acyloin condensations between carbonyl compounds, such as aldehydes and ketones, and the C1 moiety formyl-CoA. In this talk I will discuss the conceptualization, design and implementation of C1+BioTM 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: Commun Chem 7: 160, 2024; ACS Catal 13: 12007-12020, 2023; Nature Metabolism 3:1385-1399, 2021; Nature Chemical Biology 15:900-906, 2019.
Comment
To browse or post comments, you must log in.Log in