Discovery of a novel enzyme that allows free two amino acids to be directly connected

Peptides are short polymers formed from the connecting of amino acids. The distinction is that peptides are short and polypeptides/proteins are long. "Di-peptide" is composed of two amino acids. Kyowa Hakko Bio discovered a novel enzyme from Bacillus subtilis that allows free two amino acids to be directly connected. The enzyme accepts a wide variety of L-amino acids so that it synthesizes many kinds of different dipeptides.

Establishment a novel industrial process for dipeptides manufacturing

There have been several ways to produce dipeptides that were complicated and costly. A novel cost-effective and epoch-making manufacturing process for dipeptides could be realized by the combination of our novel dipeptide forming enzyme directly connecting amino acids and our traditional technology of amino acid fermentation. Moreover the characteristics of our enzyme make it possible to expand the variety of dipeptide manufacturing.

The first example of our process is for alanylglutamine (AlaGln) manufacturing. L-glutamine (Gln) is difficult to use as a component of solutions due to its heat- or acid-lability despite its nutritional importance, but the Gln-containing dipeptide L-alanyl-L-glutamine (Ala-Gln) overcomes the drawbacks and serves as a source of Gln and is expected to use as a component of medical or nutritional fields.

Dipeptide World

Dipeptides are able to be widely applicable due to the characteristic, which cannot be found in the corresponding amino acids. In addition to these physico-chemical features, it was revealed that certain kinds of dipeptides have unique physiological functions. And our novel process can supply dipeptides at low cost and can make their use spread.

Kyowa Hakko Bio treats dipeptides as amino acids in the next generation beyond the limitation of amino acids, and intends to collaborate with many researchers and companies to explore "dipeptide world".

Reference

1. Tabata K. Ikeda H. and Hashimoto S., ywfE in Bacillus subtilis codes for a novel enzyme, L-amino acid ligase, J. Bacteriol., 187, 5195-5202 (2005).
2. Tabata K. and Hashimoto S., Fermentative production of L-alanyl-L-glutamine by a metabolically engineered Escherichia coli strain expressing L-amino acid alpha-ligase, Appl. Environ. Microbiol., 73, 6378-6385 (2007).
3. Senoo A. Tabata K. Yonetani Y. and Yagasaki M., Identification of novel L-amino acid α-ligase through Hidden Markov Model based profile analysis, Biosci. Biotechnol. Biochem. , in press.
4. Hayashi　M, Tabata K, Yagasaki M and Yonetani Y, Effect of multidrug-efflux transporter genes on dipeptide resistance and overproduction in Escherichia coli, FEMS Microbiol. Lett. , in press.