BioPhenolics Co. aims at mass production of dozens of aromatic chemicals using “smart cells”

https://bio.nikkeibp.co.jp/atcl/column/16/021500017/090500297/

https://bio-phenolics.com/?page_id=68

BioPhenolics is a startup from the University of Tsukuba that is conducting research and development of technology to produce aromatic hydrocarbon chemicals with benzene rings using improved microorganisms (“smart cells”).
Currently, BioPhenolics has a pipeline of more than 10 chemical products that it is independently researching and developing, and when combined with the 10 or more products that Professor Takatani is researching, there are about 30 products in total. The bacterial strains used are E. coli and other industrial microorganisms.

Examples of chemical products that can be produced by microorganisms  include protocatechuic acid and derivatives such as catechol. Protocatechuic acid is a relatively expensive chemical that trades for around $100 per kg, but the global market is said to be only around 600 million yen. On the other hand, catechol is known as a cheap aromatic chemical, costing around $5 per kg, and the market is estimated to be worth 30 billion to 40 billion yen. In addition, there are prospects for the development of smart cells that synthesize parahydroxybenzoic acid. This can be easily converted into derivatives used as preservatives (market of about 200 billion yen) and into phenol, which is a typical general-purpose bulk product (market of 1.8 trillion yen worldwide).

The company also has a pipeline of nitrogen-containing aromatics such as aniline compounds and pyrazine compounds, which can meet the various needs of chemical companies.

BioPhenolics’ microbial breeding technology uses homologous recombination of E. coli and other bacteria. A plasmid is delivered into the bacterial body by electroporation, and the desired gene is inserted into the genome and expressed. “Although this technology has been around for a long time, we have accumulated know-how such as how to design plasmids to insert the desired gene, and it is possible to obtain the desired microorganism without using genome editing technology such as CRISPR which is expensive. There is no need to pay a license fee”.

Bioinformatics technology is used to find enzymes that can be used to construct metabolic pathways from the vast number of enzyme families reported in public databases. T

BioPhenolics’ selling point is that it not only handles microbial breeding but also production process development. In addition to the performance of microorganisms, the key to smart cell production is to combine various condition settings.

According to BioPhenolics, there is a strong demand to move away from petroleum, and chemical companies are required to take a stance on microbial bioproduction of chemicals. The future schedule is to build a bench-scale production facility with a fermentation tank of about 90L, and to start operating it in 2025 to produce protocatechuic acid and other products. In 2027, it is planned to operate a pilot plant of several kiloliters at a cost of 500 million to 1 billion yen, using funds from NEDO and investments from venture capital and from joint research with companies.

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