Insight into Isoprenoid Biosynthesis by Functional Analysis of Isoprenyl Diphosphate Synthases fromMycobacterium vanbaaleniiandMycobacterium tuberculosis

Comprehensive functional analyses ofE-isoprenyl diphosphate synthases (E-IDSs) from nonpathogenicMycobacterium vanbaaleniihave been performed. Mv0992 and Mv1577 represent a nonaprenyl diphosphate (E-C-45) synthase and a geranylgeranyl diphosphate (E-C-20) synthase, respectively. Although Mv3536 was identified as anE-C(20)synthase using a single enzyme, co-incubation of Mv3536 andZ-IDSs (Mv4662 and Mv3822) strongly suggested it releases an intermediate geranyl diphosphate (E-C-10) during a continuous condensation reaction. Mv0992 and Mv3536 functions differed from those of the previously reported pathogenicMycobacterium tuberculosishomologues Rv0562 and Rv2173, respectively. Re-analysis of Rv0562 and Rv2173 demonstrated that their functions were similar to those of Mv0992 and Mv3536 (Rv0562:E-C(45)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 theZ-IDS of the Mv3822 substrate, thereby introducing a potentially novel pathway of cyclic sesquarterpene biosynthesis.