Laying the foundation for yeast-based
opioid synthesis *IMAGES*
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NATURE CHEMICAL BIOLOGY
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Chemical biology
Embargo
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London: Monday 18 May 2015 16:00 (BST)
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New York: Monday 18 May 2015 11:00 (EDT)
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Tokyo: Tuesday 19 May 2015 00:00 (JST)
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Sydney: Tuesday 19 May 2015 01:00 (AEST)
An engineered yeast that can complete the early steps of opioid synthesis, producing (S)reticuline from glucose, is reported in a paper published online this week in Nature Chemical
Biology. Previous studies have shown that engineered yeasts can complete the final steps of
opioid synthesis. Future research to refine and bridge these pathways may eventually allow for
large-scale, low cost production of opioids.
Many, widely-used drugs are isolated or manufactured from plant extracts because their
structural complexity precludes their cost-effective synthesis in the laboratory. Systems using
engineered microbes, such as yeasts, to produce these compounds are recently becoming a
reality thanks to advances in DNA sequencing and synthetic biology. Benzylisoquinoline
alkaloids (BIAs) are a large family of plant-derived chemicals that include the compounds
morphine and codeine. They have been difficult to produce using microbes because a key
enzyme early in the pathway that can work in yeast to convert L-tyrosine to L-DOPA (a precursor
to dopamine), has not been found.
To address this, John Dueber and colleagues developed a unique colour-coded biosensor which
allowed them to identify the missing enzyme, which they then mutated to make it more
productive. They genetically engineered the yeast Saccharomyces cerevisiae to produce this
enzyme, allowing the first demonstration of the conversion of glucose to dopamine by yeast. The
authors then modified the yeast further, adding DNA from other species, so that it could perform
subsequent reactions in the pathway, eventually producing the intermediary, (S)-reticuline. One
more step is now required to bridge the two pathways.
Pamela Peralta-Yahya states in an accompanying News & Views that “Given that downstream
BIA pathway enzymes have already been shown to express in yeast, this work opens the door to
the production of complex BIAs directly from glucose.”
Article and author details
1. An enzyme-coupled biosensor enables (S)-reticuline production
in yeast from glucose
Corresponding Author
John Dueber, Berkeley
University of California Berkeley, Berkeley, California, United States
Email: jdueber@berkeley.edu, Tel: +1 510 643 4616
News & Views Author
Pamela Peralta-Yahya, Atlanta
Georgia Institute of Technology, Atlanta, Georgia, United States
Email: pperalta-yahya@chemistry.gatech.edu
DOI
10.1038/nchembio.1816
Online paper*
http://nature.com/articles/doi:10.1038/nchembio.1816
* Please link to the article in online versions of your report (the URL will go live after the embargo ends).
Geographical listings of authors
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Canada
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& United States
Image 1
Caption: Yeast cells producing the yellow beet pigment betaxanthin, which UC Berkeley researchers
used to quickly identify key enzymes in the production of benzylisoquinoline alkaloids (BIAs), the
metabolites in the poppy plant that could lead to morphine, antibiotics and other pharmaceutical agents.
Credit: William DeLoache at UC Berkeley