Production of inositol isomers by intracellular combinatorial enzymology

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K19237
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Research Field: Agricultural chemistry and related fields
• Research Institution: Kobe University
• Principal Investigator: Yoshida Ken-ichi 神戸大学, 科学技術イノベーション研究科, 教授 (20230732)
• Project Period (FY): 2017-06-30 – 2019-03-31
• Keywords: イノシトール / 枯草菌 / Geobacillus kaustophilus / combinatorial enzymology / metabolic engineering / synthetic biology

Outline of Final Research Achievements

We conducted an intracellular combinatorial enzymology in Bacillus subtilis involving multiple inositol metabolic enzymes, and in the first year, we prepared 15 combinatorial strains that combine two inositol dehydrogenases. Then, in the second year, 30 additional strains were prepared by adding inosorase enzymes derived from Bacillus subtilis and G. kaustophilus into each of the 15 strains described above. As the results, conversion of myo-inositol into scyllo-inositol and D-chiro-inositol was observed in some strains. Since the production of other inositol stereoisomers was not observed, we are currently testing other conditions using SI or DCI as a substrate as well as at higher temperatures at which the activity of the enzyme derived from G. kaustophilus is enhanced.

Free Research Field

応用微生物学

Academic Significance and Societal Importance of the Research Achievements

微生物細胞内で性質の異なる複数のアイソザイムを組み合わせるコンビナトリアル・エンザイモロジーの着想自体に前例のない斬新さがある。イノシトールの異性体は多くが希少で高価であるが、本研究の成果如何によっては安価にそれらが生産でき、それらが将来的に“希少”ではなくなる可能性がある。このようにして“希少”なイノシトール異性体の生産が可能になれば、それらに秘められた機能や用途の開発が可能となる。特に、希少イノシトイールには特異な生理活性が認められるものがあり（例えばSIはアルツハイマー病、DCIは糖尿病への適応がある）、この観点から新たな生理活性分子が発見される波及効果が見込まれる。