Geraniol 10-hydroxylase, a cytochrome P450 enzyme involved in terpenoid indole alkaloid biosynthesis.
Geraniol 10-hydroxylase (G10H) is a cytochrome P450 monooxygenase involved in the biosynthesis of iridoid monoterpenoids and several classes of monoterpenoid alkaloids found in a diverse range of plant species. Catharanthus roseus (Madagascar periwinkle) contains monoterpenoid indole alkaloids, several of which are pharmaceutically important. Vinblastine and vincristine, for example, find widespread use as anti-cancer drugs. G10H is thought to play a key regulatory role in terpenoid indole alkaloid biosynthesis. We purified G10H from C. roseus cells. Using degenerate PCR primers based on amino acid sequence information we cloned the corresponding cDNA. The encoded CYP76B6 protein has G10H activity when expressed in C. roseus and yeast cells. The stress hormone methyljasmonate strongly induced G10h gene expression coordinately with other terpenoid indole alkaloid biosynthesis genes in a C. roseus cell culture.
Collu
G
G
Division of Pharmacognosy, Leiden/Amsterdam Center for Drug Research, Leiden University, The Netherlands.
Unver
N
N
Peltenburg-Looman
A M
AM
van der Heijden
R
R
Verpoorte
R
R
Memelink
J
J
D000080462:Acyclic Monoterpenes; D000470:Alkaloids / Q000096:biosynthesis*; D000595:Amino Acid Sequence; D001483:Base Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D003517:Cyclopentanes / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism*; D008401:Gas Chromatography-Mass Spectrometry; D018506:Gene Expression Regulation, Plant / Q000187:drug effects; D006900:Hydroxylation; D019684:Magnoliopsida / Q000201:enzymology* / Q000235:genetics*; D006899:Mixed Function Oxygenases / Q000737:chemistry / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism*; D008969:Molecular Sequence Data; D054883:Oxylipins; D030821:Plants, Genetically Modified; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018749:RNA, Plant / Q000235:genetics / Q000378:metabolism; D013379:Substrate Specificity; D013729:Terpenes / Q000378:metabolism; D015003:Yeasts
D000080462:Acyclic Monoterpenes; D000470:Alkaloids; D003517:Cyclopentanes; D054883:Oxylipins; D012333:RNA, Messenger; D018749:RNA, Plant; D013729:Terpenes; C011006:jasmonic acid; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; C081675:geraniol 10-hydroxylase; C007836:geraniol