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Interactive Map of Metabolical Synthesis of Chemicals
An interactive map that compiled the chemicals produced by biological, chemical and combined reactions has been distributed on the web - A team led by Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering, organized and distributed an all-inclusive listing of chemical substances that can be synthesized using microorganisms - It is expected to be used by researchers around the world as it enables easy assessment of the synthetic pathway through the web. A research team comprised of Woo Dae Jang, Gi Bae Kim, and Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering at KAIST reported an interactive metabolic map of bio-based chemicals. Their research paper “An interactive metabolic map of bio-based chemicals” was published online in Trends in Biotechnology on August 10, 2022. As a response to rapid climate change and environmental pollution, research on the production of petrochemical products using microorganisms is receiving attention as a sustainable alternative to existing methods of productions. In order to synthesize various chemical substances, materials, and fuel using microorganisms, it is necessary to first construct the biosynthetic pathway toward desired product by exploration and discovery and introduce them into microorganisms. In addition, in order to efficiently synthesize various chemical substances, it is sometimes necessary to employ chemical methods along with bioengineering methods using microorganisms at the same time. For the production of non-native chemicals, novel pathways are designed by recruiting enzymes from heterologous sources or employing enzymes designed though rational engineering, directed evolution, or ab initio design. The research team had completed a map of chemicals which compiled all available pathways of biological and/or chemical reactions that lead to the production of various bio-based chemicals back in 2019 and published the map in Nature Catalysis. The map was distributed in the form of a poster to industries and academia so that the synthesis paths of bio-based chemicals could be checked at a glance. The research team has expanded the bio-based chemicals map this time in the form of an interactive map on the web so that anyone with internet access can quickly explore efficient paths to synthesize desired products. The web-based map provides interactive visual tools to allow interactive visualization, exploration, and analysis of complex networks of biological and/or chemical reactions toward the desired products. In addition, the reported paper also discusses the production of natural compounds that are used for diverse purposes such as food and medicine, which will help designing novel pathways through similar approaches or by exploiting the promiscuity of enzymes described in the map. The published bio-based chemicals map is also available at http://systemsbiotech.co.kr. The co-first authors, Dr. Woo Dae Jang and Ph.D. student Gi Bae Kim, said, “We conducted this study to address the demand for updating the previously distributed chemicals map and enhancing its versatility.” “The map is expected to be utilized in a variety of research and in efforts to set strategies and prospects for chemical production incorporating bio and chemical methods that are detailed in the map.” Distinguished Professor Sang Yup Lee said, “The interactive bio-based chemicals map is expected to help design and optimization of the metabolic pathways for the biosynthesis of target chemicals together with the strategies of chemical conversions, serving as a blueprint for developing further ideas on the production of desired chemicals through biological and/or chemical reactions.” The interactive metabolic map of bio-based chemicals.
Researchers Present a Microbial Strain Capable of Massive Succinic Acid Production
A research team led by Distinguished Professor Sang Yup Lee reported the production of a microbial strain capable of the massive production of succinic acid with the highest production efficiency to date. This strategy of integrating systems metabolic engineering with enzyme engineering will be useful for the production of industrially competitive bio-based chemicals. Their strategy was described in Nature Communications on April 23. The bio-based production of industrial chemicals from renewable non-food biomass has become increasingly important as a sustainable substitute for conventional petroleum-based production processes relying on fossil resources. Here, systems metabolic engineering, which is the key component for biorefinery technology, is utilized to effectively engineer the complex metabolic pathways of microorganisms to enable the efficient production of industrial chemicals. Succinic acid, a four-carbon dicarboxylic acid, is one of the most promising platform chemicals serving as a precursor for industrially important chemicals. Among microorganisms producing succinic acid, Mannheimia succiniciproducens has been proven to be one of the best strains for succinic acid production. The research team has developed a bio-based succinic acid production technology using the M. succiniciproducens strain isolated from the rumen of Korean cow for over 20 years and succeeded in developing a strain capable of producing succinic acid with the highest production efficiency. They carried out systems metabolic engineering to optimize the succinic acid production pathway of the M. succiniciproducens strain by determining the crystal structure of key enzymes important for succinic acid production and performing protein engineering to develop enzymes with better catalytic performance. As a result, 134 g per liter of succinic acid was produced from the fermentation of an engineered strain using glucose, glycerol, and carbon dioxide. They were able to achieve 21 g per liter per hour of succinic acid production, which is one of the key factors determining the economic feasibility of the overall production process. This is the world’s best succinic acid production efficiency reported to date. Previous production methods averaged 1~3 g per liter per hour. Distinguished professor Sang Yup Lee explained that his team’s work will significantly contribute to transforming the current petrochemical-based industry into an eco-friendly bio-based one. “Our research on the highly efficient bio-based production of succinic acid from renewable non-food resources and carbon dioxide has provided a basis for reducing our strong dependence on fossil resources, which is the main cause of the environmental crisis,” Professor Lee said. This work was supported by the Technology Development Program to Solve Climate Changes via Systems Metabolic Engineering for Biorefineries and the C1 Gas Refinery Program from the Ministry of Science and ICT through the National Research Foundation of Korea.
A Comprehensive Metabolic Map for Bio-Based Chemicals Production
A KAIST research team completed a metabolic map that charts all available strategies and pathways of chemical reactions that lead to the production of various industrial bio-based chemicals. The team was led by Distinguished Professor Sang Yup Lee, who has produced high-quality metabolic engineering and systems engineering research for decades, and made the hallmark chemicals map after seven years of studies. The team presented a very detailed analysis on metabolic engineering for the production of a wide range of industrial chemicals, fuels, and materials. Surveying the current trends in the bio-based production of chemicals in industrial biotechnology, the team thoroughly examined the current status of industrial chemicals produced using biological and/or chemical reactions. This comprehensive map is expected to serve as a blueprint for the visual and intuitive inspection of biological and/or chemical reactions for the production of interest from renewable resources. The team also compiled an accompanying poster to visually present the synthetic pathways of chemicals in the context of their microbial metabolism. As metabolic engineering has become increasing powerful in addressing limited fossil resources, climate change, and other environmental issues, the number of microbially produced chemicals using biomass as a carbon source has increased substantially. The sustainable production of industrial chemicals and materials has been explored with micro-organisms as cell factories and renewable nonfood biomass as raw materials for alternative petroleum. The engineering of these micro-organism has increasingly become more efficient and effective with the help of metabolic engineering – a practice of engineering using the metabolism of living organisms to produce a desired metabolite. With the establishment of systems metabolic engineering – the integration of metabolic engineering with tools and strategies from systems biology, synthetic biology and evolutionary engineering – the speed at which micro-organisms are being engineered has reached an unparalleled pace. In order to evaluate the current state at which metabolically engineered micro-organisms can produce a large portfolio of industrial chemicals, the team conducted an extensive review of the literature and mapped them out on a poster. This resulting poster, termed the bio-based chemicals map, presents synthetic pathways for industrial chemicals, which consist of biological and/or chemical reactions. Industrial chemicals and their production routes are presented in the context of central carbon metabolic pathways as these key metabolites serve as precursors for the chemicals to be produced. The resulting biochemical map allows the detection and analysis of optimal synthetic pathways for a given industrial chemical. In addition to the poster, the authors have compiled a list of chemicals that have successfully been produced using micro-organisms and a list of the corresponding companies producing them commercially. This thorough review of the literature and the accompanying analytical summary will be an important resource for researchers interested in the production of chemicals from renewable biomass sources. Metabolically engineered micro-organisms have already made a huge contribution toward the sustainable production of chemicals using renewable resources. Professor Lee said he wanted a detailed survey of the current state and capacity of bio-based chemicals production. “We are so excited that this review and poster will expand further discussion on the production of important chemicals through engineered micro-organisms and also combined biological and chemical means in a more sustainable manner,” he explained. This work was supported by the Technology Development Program to Solve Climate Changes on Systems Metabolic Engineering for Biofineries from the Ministry of Science and ICT through the National Research Foundation of Korea. For further information, Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering at KAIST ( email@example.com , Tel: +82-42-350-3930) Figure: Bio-based chemicals production through biological and chemical routes. This metabolic map describes representative chemicals that can be produced either by biological and/or chemical means. Red arrows represent chemical routes and blue arrows represent biological routes. Intermediate metabolites in the metabolism of a living organism can serve as a platform toward the production of industrially relevant chemicals. A more comprehensive map presented by the team can be found as a poster in the review.
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