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Novel Method of Haem Production Using E. coli
[ Issue 164 Page 4 ] Tuesday, September 25, 2018, 17:04:26 Sangwook Ha Senior Staff Reporter ha.sangwook@kaist.ac.kr
Distinguished Professor Sang Yup Lee

Professor Sang Yup Lee, a distinguished professor at the Department of Chemical and Biomolecular Engineering, has succeeded in improving the production methods of a crucial organometallic compound called “haem”. His paper, titled “Metabolic engineering of Escherichia coli for secretory production of free haem”, was published in Nature Catalysis on August 27. Researchers Xin Rui Zhao and Kyeong Rok Choi were also involved in this study.

Haem is a chemical substance of porphyrin origins, found almost in all eukaryotic and prokaryotic cells. It is pivotal for the transport of oxygen and the transfer of electrons necessary to generate energy inside the cell. The need for industrial haem production has been increasing around the world, with an oxidized version of haem — haemin — needed as a cure for acute porphyria and haem itself used in many dietary and health supplements. Haem is also essential to the flavoring of artificial meat in order to provide its quintessential meat flavor.

The research done by Professor Lee developed a method of using E. coli strains to produce extracellular haem. It is the first reported method to produce haem outside a cell using E. coli. Previous research involving E. coli to produce haem had always required an additional step to separate the haem from the cell. This extraction step usually resulted in extremely low yields, often in the order of milligrams. Also, the standard haem production procedure required organic solvents, which not only are inefficient, but also results in significant environmental costs.

The first step to synthesizing haem starts with the biosynthesis of 5-aminoevulinate (ALA). The two existing pathways for ALA synthesis, C4 and C5, were compared; the C5 pathway had not been previously examined for the production of haem using E. coli. The C5 path was found to be superior in speed and the metabolic genes of the C5 pathway were emphasized. Including the other pathways involved in haem production, the biosynthesis was optimized by varying the relevant gene expression levels. Additionally, the yfeX gene — a gene that causes haem degradation — was disrupted.

The resulting engineered strain deposited successfully increased the amount of secreted free haem.

Professor Lee commented, “Sustainability and environmental friendliness of the chemical industry are key agendas for every nation. We are researching methods to bio-synthesize high concentration yields with high productivity. This new technology, which extracts two thirds of the produced haem naturally outside the cell, will serve as an opportunity to move the biochemical industry forward in this direction.”

This research was funded by the Ministry of Science, ICT and Future Planning’s Technology Development Program to Solve Climate Changes on Systems Metabolic Engineering for Bio Refineries through the National Research Foundation.

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