Aza-tryptamine substrates in monoterpene indole alkaloid biosynthesis.
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.
Lee
Hyang-Yeol
HY
Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
Yerkes
Nancy
N
O'Connor
Sarah E
SE
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
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