Photo credit: www.sciencedaily.com
Advancements in Microbial Cell Factories for Sustainable Chemical Production
The pressing issues of climate change and fossil fuel depletion have intensified the global demand for sustainable methods of chemical production. As a response to these environmental challenges, there is a growing interest in microbial cell factories, which use renewable resources to produce various chemicals. Furthermore, the application of metabolic engineering technologies is essential to enhance the efficiency of these cell factories. Despite the potential benefits, significant barriers remain in selecting appropriate microbial strains and fine-tuning complex metabolic pathways for practical industrial implementation.
On March 27, KAIST (Korea Advanced Institute of Science and Technology), led by President Kwang-Hyung Lee, announced that Professor Sang Yup Lee’s research team in the Department of Chemical and Biomolecular Engineering has conducted a thorough evaluation of the production capabilities of industrial microbial cell factories. This assessment utilized advanced in silico simulations to identify optimal microbial strains for specific chemicals and effective metabolic engineering strategies.
Historically, researchers have relied on extensive biological experiments and careful validation to identify the best microbial strains and metabolic engineering strategies from a vast pool of candidates. This traditional method, however, has proven to be costly and time-consuming. The emergence of genome-scale metabolic models (GEMs), which reconstruct the metabolic networks of organisms based on their complete genomic information, now allows for systematic analysis of metabolic fluxes through computational simulations. This innovation is transforming the landscape of strain selection and metabolic pathway design.
Professor Lee’s team specifically examined the production capabilities of five key industrial microorganisms: Escherichia coli, Saccharomyces cerevisiae, Bacillus subtilis, Corynebacterium glutamicum, and Pseudomonas putida, focusing on 235 bio-based chemicals. By employing GEMs, the researchers calculated the maximum theoretical and achievable yields for each chemical under industrial conditions. This data enabled the identification of the most appropriate strains for each target compound.
The team proposed innovative strategies, such as introducing heterologous enzyme reactions from other organisms and modifying cofactor exchanges among microbes, to broaden metabolic pathways. These methods successfully enhanced yields beyond the intrinsic limitations of the microorganisms, significantly increasing the production of vital industrial chemicals including mevalonic acid, propanol, fatty acids, and isoprenoids.
In addition, the use of a computational approach to metabolically analyze fluxes allowed researchers to propose methods for enhancing microbial strains aimed at optimizing chemical production. They quantitatively mapped the connections between specific enzyme activities and the production of target chemicals, as well as the interactions between enzymes and metabolites, thereby identifying which enzyme activities should be upregulated or downregulated. These insights not only aim for high theoretical yields but also seek to maximize actual production outputs.
Dr. Gi Bae Kim, the principal author from the KAIST BioProcess Engineering Research Center, emphasized the potential of these strategies: “By incorporating metabolic pathways from other organisms and adjusting cofactor usage, we can engineer new microbial cell factories that transcend existing limitations. The methodologies uncovered in our study are integral for enhancing the cost-effectiveness and efficiency of microbial-based production processes.” Distinguished Professor Sang Yup Lee added, “This work is a critical resource in the domain of systems metabolic engineering, addressing challenges related to strain selection and pathway design, and facilitating the streamlined development of microbial cell factories. We anticipate it will greatly influence the future of technology for producing a range of eco-friendly chemicals, including biofuels, bioplastics, and materials for functional foods.”
This research received backing from projects aimed at developing platform technologies for microbial cell factories in next-generation biorefineries and advancing synthetic biology for leading the biomanufacturing industry, sponsored by the National Research Foundation and the Korean Ministry of Science and ICT, with Professor Sang Yup Lee serving as project leader.
Source
www.sciencedaily.com