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Registered: 04/02/01
Posts: 584
Alkaloid production in yeast.
    #8803417 - 08/21/08 12:49 AM (9 years, 7 months ago)

This month's Nature Chemical Biology has an interesting article.

Nature Chemical Biology 4, 524 - 525 (2008)

I'll copy paste a portion of it:

From yeast to alkaloids - pp524 - 525

Jay Keasling

One of the dreams of synthetic biology is that we will one day be able to produce any chemical in a microorganism by introducing the appropriate biosynthetic and tailoring enzymes and, in the process, replace environmentally unfriendly and/or arduous chemical synthesis routes. That dream has come closer to reality with an article from Hawkins and Smolke on the production of benzylisoquinoline alkaloids in yeast1.

And the abstract from Hawkins and Smolke.

Nature Chemical Biology 4, 564 - 573 (2008)
Published online: 10 August 2008 | doi:10.1038/nchembio.105

Production of benzylisoquinoline alkaloids in Saccharomyces cerevisiae

Kristy M Hawkins1 & Christina D Smolke1


The benzylisoquinoline alkaloids (BIAs) are a diverse class of metabolites that exhibit a broad range of pharmacological activities and are synthesized through plant biosynthetic pathways comprised of complex enzyme activities and regulatory strategies. We have engineered yeast to produce the key intermediate reticuline and downstream BIA metabolites from a commercially available substrate. An enzyme tuning strategy was implemented that identified activity differences between variants from different plants and determined optimal expression levels. By synthesizing both stereoisomer forms of reticuline and integrating enzyme activities from three plant sources and humans, we demonstrated the synthesis of metabolites in the sanguinarine/berberine and morphinan branches. We also demonstrated that a human P450 enzyme exhibits a novel activity in the conversion of (R)-reticuline to the morphinan alkaloid salutaridine. Our engineered microbial hosts offer access to a rich group of BIA molecules and associated activities that will be further expanded through synthetic chemistry and biology approaches.

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