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Structure of Papaver somniferum O-Methyltransferase 1 Reveals Initiation of Noscapine Biosynthesis with Implications for Plant Natural Product Methylation

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JournalACS Catalysis
DateAccepted/In press - 14 Mar 2019
DateE-pub ahead of print - 14 Mar 2019
DatePublished (current) - 3 May 2019
Issue number5
Volume9
Number of pages9
Pages (from-to)3840–3848
Early online date14/03/19
Original languageEnglish

Abstract

The opium poppy, Papaver somniferum, has been a source of medicinal alkaloids since the earliest civilizations, ca. 3400 B.C. The benzylisoquinoline alkaloid noscapine is produced commercially in P. somniferum for use as a cough suppressant, and it also has potential as an anticancer compound. The first committed step in the recently elucidated noscapine biosynthetic pathway involves the conversion of scoulerine to tetrahydrocolumbamine by 9-O-methylation, catalyzed by O-methyltransferase 1 (PSMT1). We demonstrate, through protein structures (obtained through rational crystal engineering at resolutions from 1.5 to 1.2 Å for the engineered variants) across the reaction coordinate, how domain closure allows specific methyl transfer to generate the product. SAM-dependent methyl transfer is central to myriad natural products in plants; analysis of amino acid sequence, now taking the three-dimensional structure of PSMT1 and low identity homologues into account, begins to shed light on the structural features that govern substrate specificity in these key, ubiquitous, plant enzymes. We propose how "gatekeeper" residues can determine acceptor regiochemistry, thus allowing prediction across the wide genomic resource.

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© 2019 American Chemical Society. This is an author-produced version of the published paper. Uploaded in accordance with the publisher’s self-archiving policy. Further copying may not be permitted; contact the publisher for details.

    Research areas

  • alkaloid, enzymatic catalysis, enzyme, medicinal plants, poppy, three-dimensional structure

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