Zingiber zerumbet CYP71BA1 catalyzes the conversion of α-humulene to 8-hydroxy-α-humulene in zerumbone biosynthesis.
Plant cytochrome P450s are involved in the biosynthesis of various classes of secondary metabolites. To elucidate the biosynthesis of zerumbone, a sesquiterpenoid with multiple potential anticancer properties, a family of P450 genes expressed in rhizomes of Zingiber zerumbet Smith, were cloned using a PCR-based cloning strategy. After functional expression in yeast, one of these P450s was found to convert α-humulene into 8-hydroxy-α-humulene, a proposed intermediate of zerumbone biosynthesis. This P450 has been designated CYP71BA1, a new member of the CYP71 family. CYP71BA1 transcripts were detected almost exclusively in rhizomes and showed a similar expression pattern to ZSS1 transcripts during rhizome development. Coexpression of a gene cluster encoding four enzymes of the mevalonate pathway with CYP71BA1 and ZSS1 in Escherichia coli leads to the production of 8-hydroxy-α-humulene in the presence of mevalonate, suggesting the possibility of microbial production of this zerumbone intermediate from a relatively simple carbon source by metabolic engineering.
Yu
Fengnian
F
Department of Bioscience, Graduate School of Agriculture, Kinki University, Nakamachi, Nara, Japan.
Okamoto
Sho
S
Harada
Hisashi
H
Yamasaki
Kazuhisa
K
Misawa
Norihiko
N
Utsumi
Ryutaro
R
D057005:Bioengineering / Q000379:methods*; D003001:Cloning, Molecular; D016000:Cluster Analysis; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D004926:Escherichia coli; D020939:Zingiber officinale / Q000737:chemistry / Q000201:enzymology*; D008798:Mevalonic Acid / Q000378:metabolism; D015394:Molecular Structure; D000081222:Monocyclic Sesquiterpenes; D010802:Phylogeny; D027343:Rhizome / Q000378:metabolism*; D012717:Sesquiterpenes / Q000737:chemistry / Q000378:metabolism*; D058615:Synthetic Biology / Q000379:methods*; D015003:Yeasts
D017931:DNA Primers; D018076:DNA, Complementary; D000081222:Monocyclic Sesquiterpenes; D012717:Sesquiterpenes; C403304:zerumbone; C042686:humulene; D003577:Cytochrome P-450 Enzyme System; D008798:Mevalonic Acid