Research and development

Biotechnology

Our company provides cost-competitive processes

Technical overview

Our company provides cost-competitive processes using biological catalyst such as microorganisms and enzymes based on the four core-technologies.

  • Route design

  • Enzyme screening

  • Enzyme engineering

  • Process optimization

①Route design

Our company has a great deal of experience planning synthetic routes, which combine not only multiple organic reactions, but also enzymatic reactions. We are able to use this knowledge to propose the optimal route for a particular synthesis.

②Enzyme screening

It is possible to screen for enzymes that catalyze a particular reaction using our extensive enzyme library and microorganism library.

③Enzyme engineering

We are able to improve the enzymatic activity or selectivity in a selected process over a short period of time by selecting effective region of an enzyme to be altered, using molecular modeling and our high-throughput evaluation system.

④Process optimization

Our company can design and scale-up an optimized process, which fits the properties of the substrate and enzyme/biocatalyst used. We can optimize processes to have higher production efficiency and high cost performance by improving the stability and activity of enzymes using the reaction conditions with feedback obtained from the challenges discovered during the enzyme engineering step in the process design/planning stage.

Technological applications

①Enzyme screening/improvement technology

When establishing a production route for (1R, 2S)-ethyl 1-amino-2-vinylcyclopropanecarboxylate hemisulfate (VCPA), a pharmaceutical intermediate, we discovered an esterase that enabled the synthesis of the desired monoester starting from a racemic mixture.

Basic concept

Basic concept

A molecular model of the substrate/enzyme complex was constructed and a subsequent screening process was carried out, which identified enzymes with four amino acid substitutions near the active site.

As a result, we introduced mutations at these four points to develop an improved enzyme, which not only has increased optical selectivity in the hydrolysis reaction, but also recognized the differences in the stereochemistry at the position. Consequently, we were able to use the enzyme to prepare solely the desired isomer from the four possible isomers.

Wild type、Optimized mutant

②Hydroxylated amino acid synthesis technology

Using our company’s hydroxylase library, it is possible to introduce hydroxyl groups at specific locations with high stereoselectivity on amino acid substrates such as cyclic imino acids, basic amino acids, and aliphatic amino acids.

Our proprietary amino acid hydroxylase library

Biology laboratory equipment

Reaction/technology

Our biology laboratory is equipped to perform reactions that employ biological catalysis using genetically modified microorganisms. We provide support for industrial production by identifying the challenges associated with scale-up and provide solutions to address them.

Equipment

Culture equipment

Jar fermenters (30 L, 3 L, and 1 L), shaker, incubator, biological safety cabinet, and autoclave.

Purification apparatus

Ultrafiltration and microfiltration system (15 mL–30 L scale), sonicator, and high pressure homogenizer.

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