Insight into C35 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, (14E)- and (14Z)-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.
Sato
Tsutomu
T
Department of Applied Biological Chemistry, Faculty of Agriculture, Graduate School of Science and Technology, Niigata University, 8050 Ikarashi-2, Niigata 950-2181, Japan. satot@agr.niigata-u.ac.jp
Takizawa
Kazuo
K
Orito
Yuriko
Y
Kudo
Hanayo
H
Hoshino
Tsutomu
T
D003500:Cyclization; D004122:Dimethylallyltranstransferase / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D009161:Mycobacterium / Q000201:enzymology*; D011994:Recombinant Proteins / Q000145:classification / Q000302:isolation & purification / Q000378:metabolism; D013237:Stereoisomerism; D013379:Substrate Specificity; D013729:Terpenes / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism*
D011994:Recombinant Proteins; D013729:Terpenes; C548353:heptaprenylcycline B; D004122:Dimethylallyltranstransferase