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Extending the biosynthetic pathway by microbial synthesis

Researchers report a novel strategy for the microbial production of multiple short-chain primary amines through bacterial synthesis

Metabolism engineers at KAIST for the first time introduced the bio-production of many short-chain elemental amines that have a wide range of applications in the chemical industries. The research team led by Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering designed novel biosynthesis pathways for short-chain primary amines by combining biosynthesis and precursor selection step.

The research team verified the newly designed pathways by confirming the in vivo production of ten short chain elemental amines through the provision of precursors. Moreover, Escherichia coli strains were metabolically designed to produce three proof-of-concept short-chain primary amines from glucose, demonstrating the potential for bio-production of diverse short-chain primary amines from renewable resources. The research team said that this study expands the strategy of systematic design of biosynthesis pathways to produce a range of related chemicals as evidenced by several short chain elemental amines as examples.

Currently, most of the industrial chemicals used in our daily life are produced from petroleum-based products. However, there are many serious issues with the petroleum industry such as depletion of fossil fuel reserves and environmental problems including global warming. To solve these problems, sustainable production of chemicals and industrial materials is being explored with microorganisms such as cell factories and renewable non-food biomass as raw materials as an alternative to petroleum-based products. Engineering these microorganisms are becoming increasingly more efficient and effective with the help of systems metabolism engineering – the practice of engineering an organism’s metabolism toward producing the desired metabolite. In this regard, the number of chemicals produced using biomass as a raw material has increased significantly.

Although the range of chemicals produced using microorganisms continues to expand through advances in systems metabolism engineering, biological production of short-chain primary amines despite their industrial importance has yet to be reported. Short chain primary amines are chemicals that contain an alkyl or aryl group instead of a hydrogen atom in ammonia with carbon chain lengths ranging from C1 to C7. Short-chain primary amines have a wide range of applications in the chemical industry, for example, as precursors for drugs (for example, anti-diabetic and hypertensive drugs), agrochemicals (for example, herbicides, fungicides, and insecticides) and solvents and vulcanizing accelerators for rubber. And plasticizers. The market size of primary short-chain amines was estimated to be over US $ 4 billion in 2014.

The main reason why the biosynthetic production of short-chain primary amines was not yet possible has been the unknown biosynthetic pathways. Therefore, the team designed biosynthesis pathways for short-chain primary amines by combining biosynthesis and precursor selection step. The biosynthesis of the biosynthesis pathway allowed for the systematic design of the biosynthesis pathway of short-chain primary amines using a set of biochemical reaction rules describing the patterns of chemical transformation between the substrate and product molecules at the atomic level.

These multiple precursors predicted for the potential biosynthesis of each short-chain primary amine were sequentially narrowed using a precursor selection step for efficient metabolism engineering experiments.

Our research demonstrates the possibility of regenerative production of short-chain elementary amines for the first time. We are planning to increase the efficiency of production of short chain primary amines. We believe that our study will play an important role in developing sustainable and environmentally friendly biological industries and reorganizing the chemical industry, which is mandatory for solving environmental problems that threaten the survival of humanity, ”Professor Lee said.

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This paper has been published under the title “Microbial Production of Multiple Short Chain Primary Amines by Bacterial Synthesis” in Nature Communications. This work was supported by the Technology Development Program for Solving Climate Change in Metabolic Systems Engineering of Biofineries from the Ministry of Science and Information Technology and Communications through the National Research Foundation (NRF) in Korea.

About Kaist

KAIST is the first and highest ranking university of science and technology in Korea. KAIST was established in 1971 by the Korean government to educate scientists and engineers committed to industrialization and economic growth in Korea.

Since then, KAIST and its 64,739 alumni have become a gateway to advanced science, technology, innovation and entrepreneurship. KAIST has emerged as one of the most innovative universities with more than 10,000 students enrolled in five colleges and seven schools including 1,039 international students from 90 countries.

On the brink of its half-year anniversary in 2021, KAIST continues to strive to make the world better through the pursuit of education, research, entrepreneurship and globalization.

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