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The rhizome oil ofZingiber zerumbetSmith contains an exceptionally high content of sesquiterpenoids with zerumbone, a predominating potential multi-anticancer agent. Biosynthetic pathways of zerumbone have been proposed, and two genesZSS1andCYP71BA1that encode the enzymes catalyzing the first two steps have been cloned. | IFEBS Journal A short-chain dehydrogenase involved in terpene metabolism from Zingiber zerumbet Sho Okamoto1 Fengnian Yu1 z Hisashi Harada2 Toshihide Okajima3 Jun-ichiro Hattan4 Norihiko Misawa2 4 and Ryutaro Utsumi1 1 Department of Bioscience Graduate Schoolof Agriculture Kinki University Nara Japan 2 CentralLaboratories for Frontier Technology Kirin Holdings Co. Ltd. Ishikawa Japan 3 Institute of Scientific and IndustrialResearch Osaka University Japan 4 Research Institute for Bioresources and Biotechnology Ishikawa PrefecturalUniversity Japan Keywords bisubstrate short-chain dehydrogenasereductase zerumbone Zingiber zerumbet Smith ZSD1 Correspondence R. Utsumi Department of Bioscience Graduate Schoolof Agriculture Kinki University Nakamachi Nara 631-8505 Japan Fax 81 742 43 8976 Tel 81 742 43 7306 E-mail utsumi@nara.kindai.ac.jp These authors contributed equally to this work Received 27 February 2011 revised 20 May 2011 accepted 7 June 2011 doi 10.1111 j.1742-4658.2011.08211.x The rhizome oil of Zingiber zerumbet Smith contains an exceptionally high content of sesquiterpenoids with zerumbone a predominating potential multi-anticancer agent. Biosynthetic pathways of zerumbone have been proposed and two genes ZSS1 and CYP71BA1 that encode the enzymes catalyzing the first two steps have been cloned. In this paper we isolated a cDNA clone ZSD1 that encodes an alcohol dehydrogenase capable of catalyzing the final step of zerumbone biosynthesis. ZSD1 has an open reading frame of 804 bp that encodes a 267-residue enzyme with a calculated molecular mass of 28.7 kDa. After expression in Escherichia coli the recombinant enzyme was found to catalyze 8-hydroxy-a-humulene into ze-rumbone. ZSD1 is a member of the short-chain dehydrogenase reductase superfamily SDR and shares high identities with other plant SDRs involved in secondary metabolism stress responses and phytosteroid biosynthesis. In contrast to the transcripts of ZSS1 and CYP71BA1 which are almost exclusively .