Biosynthesis of a novel cyclic C35-terpene via the cyclisation of a Z-type C35-polyprenyl diphosphate obtained from a nonpathogenic Mycobacterium species.
Lipid components from 12 nonpathogenic Mycobacterium species were analysed. A novel cyclic C(35)-terpene, named heptaprenylcycline , was obtained from 3 species, while octahydroheptaprenol , which has 3 Z-double bonds, was obtained from 6 species. The amounts of and in the cultured cells increased after the 4- to 6-d stationary phase. The yield of was considerably greater at a higher temperature of 37 degrees C than at an optimal temperature of 28 degrees C, while that of remained unchanged at all temperatures. A feeding experiment with d-[1-(13)C]glucose revealed that was produced via isopentenyl diphosphate, which is a metabolite of glycolysis and the methylerythritol phosphate pathway. The conversion of octahydroheptaprenyl diphosphate to was successful by using the cell-free extracts of M. chlorophenolicum, demonstrating that is the biosynthetic intermediate of . This is the first example of the biosynthesis of a natural terpene via the cyclisation of a linear C(35)-isoprenoid. The substrate for C(35)-terpene cyclase has Z-type prenyl moieties; however, terpene cyclases usually employ E-type isoprenoids. The gene encoding the terpene cyclase that cyclises prenyl diphosphate containing Z-double bonds as the natural substrate has not yet been detected. Despite a careful search using the FASTA3 program, we could not detect any gene that is homologous to the known diphosphate-triggered type of mono-, sesqui- and diterpene cyclases in the genome of M. vanbaalenii, the DNA sequence of which has recently been elucidated. This suggests that a novel type of terpene cyclase might exist in the nonpathogenic Mycobacterium species.
Department of Applied Biological Chemistry, Faculty of Agriculture, and Graduate School of Science and Technology, Niigata University, Ikarashi, Niigata 950-2181, Japan. satot@agr.niigata-u.ac.jp
Tsutomu
T
Sato
Atsushi
A
Kigawa
Ryosuke
R
Takagi
Tomomi
T
Adachi
Tsutomu
T
Hoshino
D003470:Culture Media; D003500:Cyclization; D011756:Diphosphates / Q000737:chemistry* / Q000378:metabolism*; D008055:Lipids / Q000032:analysis; D009161:Mycobacterium / Q000737:chemistry* / Q000378:metabolism*; D014315:Triterpenes / Q000032:analysis* / Q000302:isolation & purification / Q000378:metabolism*
D003470:Culture Media; D011756:Diphosphates; D008055:Lipids; D014315:Triterpenes