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  Silencing of tryptamine biosynthesis for production of nonnatural alkaloids in plant culture

Runguphan, W., Maresh, J. J., & O'Connor, S. E. (2009). Silencing of tryptamine biosynthesis for production of nonnatural alkaloids in plant culture. Proceedings of the National Academy of Sciences of the United States of America, 106(33), 13673-13678. doi:10.1073/pnas.0903393106.

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Item Permalink: https://hdl.handle.net/21.11116/0000-0002-BE1A-C Version Permalink: https://hdl.handle.net/21.11116/0000-0009-3D4F-C
Genre: Journal Article

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 Creators:
Runguphan, Weerawat, Author
Maresh, Justin J., Author
O'Connor, Sarah E.1, Author           
Affiliations:
1External Organizations, ou_persistent22              

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 Abstract: Natural products have long served as both a source and inspiration for pharmaceuticals. Modifying the structure of a natural product often improves the biological activity of the compound. Metabolic engineering strategies to ferment “unnatural” products have been enormously successful in microbial organisms. However, despite the importance of plant derived natural products, metabolic engineering strategies to yield unnatural products from complex, lengthy plant pathways have not been widely explored. Here, we show that RNA mediated suppression of tryptamine biosynthesis in Catharanthus roseus hairy root culture eliminates all production of monoterpene indole alkaloids, a class of natural products derived from two starting substrates, tryptamine and secologanin. To exploit this chemically silent background, we introduced an unnatural tryptamine analog to the production media and demonstrated that the silenced plant culture could produce a variety of novel products derived from this unnatural starting substrate. The novel alkaloids were not contaminated by the presence of the natural alkaloids normally present in C. roseus. Suppression of tryptamine biosynthesis therefore did not appear to adversely affect expression of downstream biosynthetic enzymes. Targeted suppression of substrate biosynthesis therefore appears to be a viable strategy for programming a plant alkaloid pathway to more effectively produce desirable unnatural products. Moreover, although tryptamine is widely found among plants, this silenced line demonstrates that tryptamine does not play an essential role in growth or development in C. roseus root culture. Silencing the biosynthesis of an early starting substrate enhances our ability to harness the rich diversity of plant based natural products.

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 Dates: 2009-08-18
 Publication Status: Issued
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 Identifiers: Other: SOC073
DOI: 10.1073/pnas.0903393106
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Title: Proceedings of the National Academy of Sciences of the United States of America
  Other : Proc. Acad. Sci. USA
  Other : Proceedings of the National Academy of Sciences of the USA
  Abbreviation : PNAS
Source Genre: Journal
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Publ. Info: Washington, D.C. : National Academy of Sciences
Pages: - Volume / Issue: 106 (33) Sequence Number: - Start / End Page: 13673 - 13678 Identifier: ISSN: 0027-8424
CoNE: https://pure.mpg.de/cone/journals/resource/954925427230