Substrate Flexibilities of Norbelladine Synthase and Noroxomaritidine/ Norcraugsodine Reductase for Hydroxylated and/or Methoxylated Aldehydes

Saw Yu Yu Hnin, Yu Nakashima, Hiroyuki Morita*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Amaryllidaceae alkaloids are structurally diverse natural products with a wide range biological properties, and based on the partial identification of the biosynthetic enzymes, norbelladine would be a common intermediate in the biosynthetic pathways. Previous studies suggested that norbelladine synthase (NBS) catalyzed the condensation reaction of 3,4-di-hydroxybenzaldehyde and tyramine to form norcraugsodine, and subsequently, noroxomaritidine/norcraugsodine reductase (NR) catalyzed the nicotinamide adenine dinucleotide phosphate (NADPH)-dependent reduction of norcraugsodine to generate norbelladine. However, recent studies have highlighted possible alternative Amaryllidaceae alkaloid biosynthetic pathways via the formation of isovanillin and vanillin from the 4-O- and 3-O-methylation reactions of 3,4-dihydroxy-benzaldehyde, respectively. Herein, we focused on NpsNBS and NpsNR, which were initially identified from Narcissus pseudonarcissus, and explored their substrate recognition tolerance by performing condensation reactions of tyramine with various benzaldehyde derivatives, to shed light on the Amaryllidaceae alkaloid biosynthetic pathway from the viewpoint of the enzymatic properties. The assays revealed that both NpsNBS and NpsNR lacked the abilities to produce 4′-O- and 3′-O-methylnorbelladine from isovanillin and vanillin with tyramine, respectively. These observations thus suggested that Amaryllidaceae alkaloids are biosynthesized from norbelladine, formed through the condensation/reduction reaction of 3,4-dihydroxybenzaldehyde with tyramine.

Original languageEnglish
Pages (from-to)507-511
Number of pages5
JournalChemical and Pharmaceutical Bulletin
Volume72
Issue number5
DOIs
StatePublished - 2024

Keywords

  • Amaryllidaceae alkaloid
  • norbelladine synthase
  • norbelladine synthase (NBS)
  • noroxomaritidine/norcraugsodine reductase
  • noroxomaritidine/norcraugsodine reductase (NR)

ASJC Scopus subject areas

  • General Chemistry
  • Drug Discovery

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