Crag News

Improved itaconic acid production by using synthetic biology

Crystal structure of MmgE that has been used to choose the target residues for mutagenesis.
Crystal structure of MmgE that has been used to choose the target residues for mutagenesis.

Researchers at CRAG, in collaboration with researchers at Pohang University of Science and Technology in Korea, have recently published a work in Nature Communications journal revealing a new strategy to improve itaconic acid production through synthetic biology technology. Itaconic acid is used as a raw material for manufacturing cosmetics and antibacterial agents, as well as various plastics including biodegradable polymers. Despite such high potential, its use is limited by insufficient production technologies and high production costs. This novel discovery demonstrates the potential and wide applicability of synthetic biology tools to produce itaconic acid in a more efficient manner.

Itaconic acid is industrially produced using fungi by the fermentation of carbohydrates, such as glucose or molasses. Its biosynthesis is limited by enzymatic competition in the cells, which fungi overcome by using physical separation with a membranous organelle. However, working with fungi entails increased costs due to expensive raw materials and complicated processes, while bacteria like Escherichia coli, which are normally used as industrial microorganisms, grow using low-cost raw materials and are easy to cultivate. Despite such advantages, bacteria have difficulties in efficiently producing itaconic acid due to the absence of membranous organelles.

In this work, researchers have used synthetic biology tools to create a new metabolic pathway that produces itaconic acid without the need of the physical separation in different cellular compartments. This technology enables the development of a microbial cell factory capable of producing itaconic acid in E. coli using low-cost raw materials.

«Our work opens the possibility of a more economically viable way of mass-producing itaconic acid», points out Jae-Seong Yang, researcher at CRAG and one of the corresponding authors of the study.

Due to concerns about climate change, biorefinery technology that uses microorganisms to convert biomass into beneficial byproducts (such as chemicals) is seeking to replace the existing petrochemical-based compound production, and this discovery contributes its grain of sand towards the establishment of a carbon-neutral society.

Reference article

Dae-Yeol Ye, Myung Hyun Noh, Jo Hyun Moon, Alfonsina Milito, Minsun Kim, Jeong Wook Lee, Jae-Seong Yang, Gyoo Yeol Jung. Kinetic compartmentalization by unnatural reaction for itaconate production. Nature Communications, 12 Sep 2022 (DOI: 10.1038/s41467-022-33033-1)

About the authors and funding of the study

This research was supported by the C1 Gas Refinery Program (NRF-2018M3D3A1A01055754, G.Y.J.) and the grants (NRF2019R1A2C2084631, G.Y.J. and NRF-2021R1A6A3A03043982, M.H.N.) from the National Research Foundation (NRF) of Korea. We also acknowledge that this work was supported by grants SEV‐2015‐0533 and CEX2019-000902-S funded by MCIN/AEI/10.13039/501100011033, and by the CERCA Programme / Generalitat de Catalunya (J.-S.Y.). Also, this project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie SkłodowskaCurie grant agreement No 945043 (A.M.).