[ODP4F] f. Microbial Metabolism

[ODP-076] Functional analysis of isoprenyl diphosphate synthases from mycobacteria

○Tohru Abe, Sadamu Ozaki, Daijiro Ueda, Tsutomu Sato (Grad. Sch. Sci. Technol., Niigata Univ.)

Comprehensive functional analyses of E-isoprenyl diphosphate synthases (E-IDSs) from nonpathogenic Mycobacterium vanbaalenii have been performed. Mv0992 and Mv1577 represent a nonaprenyl diphosphate (E-C₄₅) synthase and a geranylgeranyl diphosphate (E-C₂₀) synthase, respectively. Although Mv3536 was identified as an E-C₂₀ synthase using a single enzyme, coincubation of Mv3536 and Z-IDSs (Mv4662 and Mv3822) strongly suggested it releases an intermediate geranyl diphosphate (E-C₁₀) during a continuous condensation reaction. Mv0992 and Mv3536 functions differed from those of the previously reported pathogenic Mycobacterium tuberculosis homologues Rv0562 and Rv2173, respectively. Re-analysis of Rv0562 and Rv2173 demonstrated that their functions were similar to those of Mv0992 and Mv3536 (Rv0562: E-C₄₅ synthase; Rv2173: E-C_10–15 synthase). The newly proposed functions of Rv0562 and Rv2173 would be in the biosynthesis of menaquinone and glycosyl carrier lipids essential for growth. Furthermore, a reduced allylic diphosphate could be used as the Z-IDS of the Mv3822 substrate, thereby introducing a potentially novel pathway of cyclic sesquarterpene biosynthesis.