Identification of a noroxomaritidine reductase with amaryllidaceae alkaloid biosynthesis related activities

Matthew B. Kilgore, Cynthia K. Holland, Joseph M. Jez, Toni M. Kutchan

Research output: Contribution to journalArticlepeer-review

31 Scopus citations


Amaryllidaceae alkaloids are a large group of plant natural products with over 300 documented structures and diverse biological activities. Several groups of Amaryllidaceae alkaloids including the hemanthamine- and crinine-type alkaloids show promise as anticancer agents. Two reduction reactions are required for the production of these compounds: the reduction of norcraugsodine to norbelladine and the reduction of noroxomaritidine to normaritidine, with the enantiomer of noroxomaritidine dictating whether the derivatives will be the crinine-type or hemanthamine-type. It is also possible for the carbon-carbon double bond of noroxomaritidine to be reduced, forming the precursor for maritinamine or elwesine depending on the enantiomer reduced to an oxomaritinamine product. In this study, a short chain alcohol dehydrogenase/reductase that co-expresses with the previously discovered norbelladine 4′-O-methyltransferase from Narcissus sp. and Galanthus spp. was cloned and expressed in Escherichia coli. Biochemical analyses and x-ray crystallography indicates that this protein functions as a noroxomaritidine reductase that forms oxomaritinamine from noroxomaritidine through a carbon-carbon double bond reduction. The enzyme also reduces norcraugsodine to norbelladine with a 400-fold lower specific activity. These studies identify a missing step in the biosynthesis of this pharmacologically important class of plant natural products.

Original languageEnglish
Pages (from-to)16740-16752
Number of pages13
JournalJournal of Biological Chemistry
Issue number32
StatePublished - Aug 5 2016


Dive into the research topics of 'Identification of a noroxomaritidine reductase with amaryllidaceae alkaloid biosynthesis related activities'. Together they form a unique fingerprint.

Cite this