Researchers develop a yeast-based platform to boost production of rare
natural molecules
Vincent Martin's team publishes a novel approach to synthesizing
essential medicines like morphine and naloxone

Date:
August 27, 2020
Source:
Concordia University
Summary:
Researchers outline a method to synthesize complex bioactive
molecules much more quickly and efficiently. Using cutting-edge
synthetic biology approaches, They were able to produce a large
amount of benzylisoquinoline alkaloid (BIA) to synthesize an
array of natural and new-to-nature chemical structures in a
yeast-based platform. This can provide a blueprint for the
large-scale production of thousands of products, including the
opioid analgesics morphine and codeine.



FULL STORY ==========================================================================
Many modern medicines, including analgesics and opioids, are derived from
rare molecules found in plants and bacteria. While they are effective
against a host of ailments, a number of these molecules have proven to be difficult to produce in large quantities. Some are so labour intensive
that it is uneconomical for pharmaceutical companies to produce them in sufficient amounts to bring them to market.


==========================================================================
In a new study published in Nature Communications, Vincent Martin
outlines a method to synthesize complex bioactive molecules much more
quickly and efficiently.

One of the principal ingredients in this new technique developed by the
biology professor and Concordia University Research Chair in Microbial Engineering and Synthetic Biology is simple baker's yeast.

The single-cell organism has cellular processes that are similar to
those of humans, giving biologists an effective substitute in drug
development research.

Using cutting-edge synthetic biology approaches, Martin and his
colleagues in Berkeley, California were able to produce a large amount
of benzylisoquinoline alkaloid (BIA) to synthesize an array of natural
and new-to-nature chemical structures in a yeast-based platform.

This, he says, can provide a blueprint for the large-scale production
of thousands of products, including the opioid analgesics morphine
and codeine.

The same is true for opioid antagonists naloxone and naltrexone, used
to treat overdose and dependence.

A long journey from gene to market Martin has been working toward this
outcome for most of the past two decades.

He began with researching the genetic code plants use to produce the
molecules used as drugs by the pharmaceutical industry. Then came
transplanting their genes and enzymes into yeast to see if production
was possible outside a natural setting. The next step is industrial
production.



==========================================================================
"We showed in previous papers that we can get milligrams of these
molecules fairly easily, but you're only going to be able to commercialize
the process if you get grams of it," Martin explains. "In principle, we
now have a technology platform where we can produce them on that scale."
This, he says, can have huge implications for a country like Canada,
which has to import most of the rare molecules used in drugs from
overseas. That's especially relevant now, in the midst of a global
pandemic, when fragile supply chains are at risk of being disrupted.

"To me, this really highlights the importance of finding alternative
biotech- type processes that can be developed into a homemade, Canadian pharmaceutical industry," he adds. "Many of the ingredients we use
today are not very difficult to make. But if we don't have a reliable
supply process in Canada, we have a problem." Healthy savings Martin
admits he is curious to see where the technology leads us. He believes researchers can and will use the new platform for the commercialization
and discovery of new drugs.

"We demonstrate that by using this platform, we can start building what
is called new-to-nature molecules," he says. "By experimenting with
enzymes and genes and the way we grow things, we can begin making these
into tools that can be used in the drug discovery process. We can access
a whole new structural space." This study was financially supported by
a Natural Sciences and Engineering Research Council of Canada (NSERC) Industrial Biocatalysis Grant, an NSERC Discovery Grant and by River
Stone Biotech ApS.


========================================================================== Story Source: Materials provided by Concordia_University. Original written
by Patrick Lejtenyi. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Michael E. Pyne, Kaspar Kevvai, Parbir S. Grewal, Lauren Narcross,
Brian
Choi, Leanne Bourgeois, John E. Dueber, Vincent J. J. Martin. A
yeast platform for high-level synthesis of tetrahydroisoquinoline
alkaloids.

Nature Communications, 2020; 11 (1) DOI: 10.1038/s41467-020-17172-x ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/08/200827155005.htm

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