[ODP10] 3. 生理・構造-a. 代謝・生合成・メタボローム

[ODP-042] 抗酸菌の新しいタイプのZ,E混成型プレニル基還元酵素の同定と機能解析

阿部 透^1,2,3，袴田 真理子²，西山 晃史²，立石 善隆²，松本 壮吉²，邊見 久³，上田 大次郎¹，佐藤 努¹ (¹新潟大・院・自然，²新潟大・医・細菌学，³名大・院・生命農)

Isoprenoid with reduced Z,E-mixed prenyl groups have been found in a wide range of organisms. As an enzyme that reduces Z,E-mixed prenyl groups, only polyprenol reductases (PR-Dol) involved in dolichol biosynthesis have been identified to date. Although C₃₅-isoprenoids with reduced Z,E-mixed prenyl groups have also been found in mycobacteria, Z,E-mixed heptaprenyl reductase (HepR) has been unidentified. In this study, in vitro enzymatic assay and in vivo repression analysis using CRISPR interference revealed that the GGR homolog, which reacts with an all-E prenyl group as a substrate, is HepR. Therefore, it was demonstrated that some GGR homologs function as Z,E-mixed prenyl reductase. This is the first identification of a new type of Z,E-mixed prenyl reductase that has no sequence homology with PR-Dol. The substrate specificity of HepR was significantly different from that of GGR, suggesting that HepR has a new recognition site for substrate. The BLAST search revealed that HepR homologs are widely distributed in mycobacterial species. Analysis of lipid components revealed that HepR metabolites are also produced in pathogens such as Mycobacteroides abscessus for the first time. Our results will provide important insights not only for the discovery of new reduced Z,E-mixed isoprenoids, but also for the elucidation of new physiological functions of reduced isoprenoids in vivo.