Discovery of a Short‐Chain Dehydrogenase from Catharanthus roseus that Produces a New Monoterpene Indole Alkaloid. (22nd March 2018)

• Record Type: Journal Article
• Authors: Stavrinides, Anna K.; Tatsis, Evangelos C.; Dang, Thu‐Thuy; Caputi, Lorenzo; Stevenson, Clare E. M.; Lawson, David M.; Schneider, Bernd; O'Connor, Sarah E.
• Is Part Of: Chembiochem. Volume 19:Number 9(2018)
• Page Start: 940
• Page End: 948
• Publication Date: 2018-03-22
• Subjects: alkaloids -- biosynthesis -- natural products -- reduction -- short-chain dehydrogenases; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1002/cbic.201700621
• Languages: English
• ISSNs: 1439-4227

Abstract

Abstract: Plant monoterpene indole alkaloids, a large class of natural products, derive from the biosynthetic intermediate strictosidine aglycone. Strictosidine aglycone, which can exist as a variety of isomers, can be reduced to form numerous different structures. We have discovered a short‐chain alcohol dehydrogenase (SDR) from plant producers of monoterpene indole alkaloids ( Catharanthus roseus and Rauvolfia serpentina ) that reduce strictosidine aglycone and produce an alkaloid that does not correspond to any previously reported compound. Here we report the structural characterization of this product, which we have named vitrosamine, as well as the crystal structure of the SDR. This discovery highlights the structural versatility of the strictosidine aglycone biosynthetic intermediate and expands the range of enzymatic reactions that SDRs can catalyse. This discovery further highlights how a sequence‐based gene mining discovery approach in plants can reveal cryptic chemistry that would not be uncovered by classical natural product chemistry approaches. Abstract : Cryptic and unnatural natural products : A short‐chain alcohol dehydrogenase from plant producers of monoterpene indole alkaloids ( C. roseus and R. serpentina ) reduces strictosidine aglycone to form an alkaloid that does not correspond to any previously reported compound.