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. 2009 Dec 24;16(12):1225-9.
doi: 10.1016/j.chembiol.2009.11.016.

Aza-tryptamine substrates in monoterpene indole alkaloid biosynthesis

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Aza-tryptamine substrates in monoterpene indole alkaloid biosynthesis

Hyang-Yeol Lee et al. Chem Biol. .

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.

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Figures

Figure 1
Figure 1
The aza-indole moiety (highlighted in red) in natural and synthetic compounds. A. Aza-indoles in natural products. B. Aza-indole moiety in an indole natural product analog. C. Synthetic pharmaceutically important compounds containing an aza-indole group.
Figure 2
Figure 2
Synthesis of aza-tryptamine compounds 14.
Figure 3
Figure 3
Figure 3A. Reaction of aza-tryptamine compounds 14 in a Pictet-Spengler reaction. B. Formation of downstream alkaloid and aza-alkaloid products.
Figure 4
Figure 4
LC-MS spectra showing production of new compounds by Catharanthus roseus when supplemented with deglycosylated strictosidine derived from 1 and 4. Starred peaks indicate compounds found only in cultures supplemented with deglycosylated strictosidine derived from 1 or 4. LC-MS spectra showing the results of feeding deglycosylated strictosidine 11 derived from natural tryptamine 5 to cell cultures are shown in the Supporting Information.

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References

    1. Adler TK, Albert A. The biological and physical properties of the azaindoles. J Med Chem. 1963;6:480–483. - PubMed
    1. Bernhardt P, McCoy E, O’Connor SE. Rapid identification of enzyme variants for reengineered alkaloid biosynthesis in periwinkle. Chem Biol. 2007;14:888–897. - PMC - PubMed
    1. Bernhardt P, Yerkes N, O’Connor SE. Bypassing stereoselectivity in the early steps of alkaloid biosynthesis. Org Biomol Chem. 2009;7:4166–4168. - PMC - PubMed
    1. Hemscheidt T, Zenk MH. Partial purification and characterization of a NADPH dependent tetrahydroalstonine synthase from Catharanthus roseus cell suspension cultures. Plant Cell Rep. 1985;4:216–219. - PubMed
    1. Klapars A, Buchwald SL. Copper-catalyzed halogen exchange in aryl halides: An aromatic Finkelstein reaction. J Am Chem Soc. 2002;124:14844–14845. - PubMed

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