Insight into C 35 terpene Biosyntheses by Nonpathogenic Mycobacterium Species: Functional Analyses of Three Z ‐Prenyltransferases and Identification of Dehydroheptaprenylcyclines

Nonpathogenic Mycobacterium species produce rare cyclic C 35 terpenes that are biosynthesized by cyclization of Z ‐type C 35 polyprenyl diphosphate. To provide deeper insight into the biosynthesis of C 35 terpenes, we carried out functional analyses of three Z ‐prenyltransferase homologues in M. vanbaalenii identified by genomic analysis. Mvan_3822, a novel bifunctional Z ‐prenyltransferase, biosynthesizes C 35 ‐heptaprenyl diphosphate as a main product from ( E , E )‐farnesyl diphosphate ( E , E ‐FPP) and ( E , E , E )‐geranylgeranyl diphosphate ( E , E , E ‐GGPP), but produces a C 50 ‐decaprenyl diphosphate from geranyl diphosphate. Mvan_1705 is a novel Z , E , E ‐GGPP synthase. In addition, novel cyclic C 35 terpenes, (14 E )‐ and (14 Z )‐dehydroheptaprenylcycline, were identified as minor metabolites in nonpathogenic Mycobacterium cells. C 35 terpenes could be biosynthesized by two routes, in which E and Z geometric isomers of heptaprenyl diphosphate are produced from E , E ‐FPP and E , E , E ‐GGPP, and the prenylreductase responsible for the biosynthesis of C 35 terpenes could reduce both E and Z prenyl residues.