Industrial-level production of bio-succinic acid from a renewable resource using a metabolically-engineered microorganism

A research group led by Professor Sang Yup Lee has developed a bioprocess employing a metabolically-engineered microorganism that allows industrial-level production of bio-succinic acid from a renewable resource. Succinic acid serves as a precursor for industrial chemicals and biodegradable polymers.

Article | Spring 2021

In recent years, fossil-resource-dependent chemical processes are being shifted toward more sustainable processes for bio-based production of chemicals and materials from renewable resources due to increasing concerns of climate change and other environmental problems. Currently, hundreds of different chemicals and materials can be synthesized using biological reactions. However, very few have yet succeeded in commercialization due to the difficulty in developing a cost-effective bioprocess that is equally competitive to that of the petrochemical process. Succinic acid, representing one of the few successful cases, is being produced in several plants established by companies such as Ajinomoto, BASF, Kawasaki Kasei Chemicals, and Reverdia. Succinic acid is used as a surfactant, ion chelator, additive in agricultural and food, and ingredient in pharmaceutical industries. The demand of succinic acid as a platform chemical is expected to rapidly increase to an anticipated market size of >700,000 tons per year by 2021. A much bigger market of succinic acid is expected as succinic acid serves a precursor for numerous industrial chemicals including adipic acid (precursor for nylon), 1,4-butanediol (precursor for Spandex), tetrahydrofuran (solvent), and gamma-butyrolactone (precursor for pesticide and herbicide). Furthermore, its use can be extended to the synthesis of bio-based and/or biodegradable polymers such as polyesters (polybutylene succinate) and polyamides (nylons).

In this study, a highly efficient succinic-acid-producing bacterial strain was successfully developed by integrating the strategies of systems metabolic engineering with protein engineering. The structure of two key enzymes associated with succinic acid production were discovered for the first time, and an enzyme with enhanced catalytic performance was developed using protein engineering based on structural analysis. The genes associated with byproducts production in the engineered strain were deleted from the genome to enhance product yield. Finally, fed-batch fermentation of the engineered strain produced 134 g per L of succinic acid with a maximum productivity of 21 g per L per hour using glucose, glycerol, and carbon dioxide. This is the world’s best succinic acid production efficiency reported to date. Previous production methods averaged 1~3 g per L per hour. The engineered bacterial strain capable of producing industrial-level succinic acid can be further utilized as a platform strain to produce other industrially competitive bio-based chemicals and materials from renewable resource and carbon dioxide.

Professor Sang Yup Lee said, “This work on 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”.
This work was published in Nature Communications on April 23, 2020 under the title, “Enhanced succinic acid production by Mannheimia employing optimal malate dehydrogenase”.

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.