title: Aza-tryptamine substrates in monoterpene indole alkaloid biosynthesis.
abstract: Biosynthetic pathways can be hijacked to yield novel compounds by introduction of novel starting materials. Here we have altered tryptamine, which serves as the starting substrate for a variety of alkaloid biosynthetic pathways, by replacing the indole with one of four aza-indole isomers. We show that two aza-tryptamine substrates can be successfully incorporated into the products of the monoterpene indole alkaloid pathway in Catharanthus roseus. Use of unnatural heterocycles in precursor-directed biosynthesis, in both microbial and plant natural product pathways, has not been widely demonstrated, and successful incorporation of starting substrate analogs containing the aza-indole functionality has not been previously reported. This work serves as a starting point to explore fermentation of aza-alkaloids from other tryptophan- and tryptamine-derived natural product pathways.
authors.affiliation: Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
authors.forename: Hyang-Yeol
authors.initials: HY
authors.lastname: Lee
authors.forename: Nancy
authors.initials: N
authors.lastname: Yerkes
authors.forename: Sarah E
authors.initials: SE
authors.lastname: O'Connor
mesh_terms: D000470:Alkaloids / Q000096:biosynthesis; D001372:Aza Compounds / Q000737:chemistry* / Q000378:metabolism; D019759:Carbon-Nitrogen Lyases / Q000378:metabolism; D030008:Catharanthus / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D005959:Glucosidases / Q000378:metabolism; D026121:Indole Alkaloids / Q000737:chemistry / Q000378:metabolism*; D007536:Isomerism; D039821:Monoterpenes / Q000737:chemistry / Q000378:metabolism*; D021241:Spectrometry, Mass, Electrospray Ionization; D014363:Tryptamines / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000470:Alkaloids; D001372:Aza Compounds; D026121:Indole Alkaloids; D039821:Monoterpenes; D014363:Tryptamines; C030820:tryptamine; D005959:Glucosidases; C456847:strictosidine glucosidase; D019759:Carbon-Nitrogen Lyases; C022684:strictosidine synthetase