{"id":26160,"date":"2015-05-21T03:09:02","date_gmt":"2015-05-21T01:09:02","guid":{"rendered":"https:\/\/renewable-carbon.eu\/news\/?p=26160"},"modified":"2015-05-20T11:50:24","modified_gmt":"2015-05-20T09:50:24","slug":"discovery-paves-way-for-homebrewed-drugs-prompts-call-for-regulation","status":"publish","type":"post","link":"https:\/\/renewable-carbon.eu\/news\/discovery-paves-way-for-homebrewed-drugs-prompts-call-for-regulation\/","title":{"rendered":"Discovery paves way for homebrewed drugs, prompts call for regulation"},"content":{"rendered":"

Fans of homebrewed beer and backyard distilleries already know how to employ yeast to convert sugar into alcohol. But a research team led by UC Berkeley bioengineers<\/a> has gone much further by completing key steps needed to turn sugar-fed yeast into a microbial factory for producing morphine and potentially other drugs, including antibiotics and anti-cancer therapeutics.<\/strong><\/p>\n

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New research may soon make growing fields of opium poppy unnecessary when it comes to the production of opiates and potentially other drugs, such as antibiotics. A team led by UC Berkeley bioengineers has completed key steps that will enable yeast to convert sugar into pharmaceuticals.<\/figcaption><\/figure>\n

Over the past decade, a handful of synthetic-biology labs have been working on replicating in microbes a complex, 15-step chemical pathway in the poppy plant to enable production of therapeutic drugs. Research teams have independently recreated different sections of the poppy\u2019s drug pathway using E. coli or yeast, but what had been missing until now were the final steps that would allow a single organism to perform the task from start to finish.<\/p>\n

In a new study appearing\u00a0today (Monday, May 18) in the advanced online publication of the journal Nature Chemical Biology<\/a>, UC Berkeley bioengineer John Dueber teamed up with microbiologist Vincent Martin at Concordia University in Montreal, to overcome that hurdle by replicating the early steps in the pathway in an engineered strain of yeast. They were able to synthesize reticuline, a compound in poppy, from tyrosine, a derivative of glucose.<\/p>\n

\u201cWhat you really want to do from a fermentation perspective is to be able to feed the yeast glucose, which is a cheap sugar source, and have the yeast do all the chemical steps required downstream to make your target therapeutic drug,\u201d said Dueber, the study\u2019s principal investigator and an assistant professor of bioengineering. \u201cWith our study, all the steps have been described, and it\u2019s now a matter of linking them together and scaling up the process. It\u2019s not a trivial challenge, but it\u2019s doable.\u201d<\/p>\n

Paving the path from plants to microbes<\/h3>\n

The qualities that make the poppy plant pathway so challenging are the same ones that make it such an attractive target for research. It is complex, but it is the foundation upon which researchers can build new therapeutics. Benzylisoquinoline alkaloids, or BIAs, are the class of highly bioactive compounds found in the poppy, and that family includes some 2,500 molecules isolated from plants.<\/p>\n

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On the right are 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 pharmaceuticals. (Photo by William DeLoache)<\/figcaption><\/figure>\n

Perhaps the best-known trail in the BIA pathway is the one that leads to the opiates, such as codeine, morphine and thebaine, a precursor to oxycodone and hydrocodone. All are controlled substances. But different trails will lead to the antispasmodic papaverine or to the antibiotic precursor dihydrosanguinarine.<\/p>\n

\u201cPlants have slow growth cycles, so it\u2019s hard to fully explore all the possible chemicals that can be made from the BIA pathway by genetically engineering the poppy,\u201d said study lead author William DeLoache, a UC Berkeley Ph.D. student in bioengineering. \u201cMoving the BIA pathway to microbes dramatically reduces the cost of drug discovery. We can easily manipulate and tune the DNA of the yeast and quickly test the results.\u201d<\/p>\n

The researchers found that by repurposing an enzyme from beets that is naturally used in the production of their vibrant pigments, they could coax yeast to convert tyrosine, an amino acid readily derived from glucose, into dopamine.<\/p>\n

With help from the lab of Concordia University\u2019s Vincent Martin, the researchers were able to reconstitute the full seven-enzyme pathway from tyrosine to reticuline in yeast.<\/p>\n

\u201cGetting to reticuline is critical because from there, the molecular steps that produce codeine and morphine from reticuline have already been described in yeast,\u201d said Martin, a professor of microbial genomics and engineering. \u201cAlso, reticuline is a molecular hub in the BIA pathway. From there, we can explore many different paths to other potential drugs, not just opiates.\u201d<\/p>\n

Red flag for regulators<\/h3>\n

The study authors noted that the discovery dramatically speeds up the clock for when homebrewing drugs could become a reality, and they are calling for regulators and law enforcement officials to pay attention.<\/p>\n

\u201cWe\u2019re likely looking at a timeline of a couple of years, not a decade or more, when sugar-fed yeast could reliably produce a controlled substance,\u201d said Dueber. \u201cThe time is now to think about policies to address this area of research. The field is moving surprisingly fast, and we need to be out in front so that we can mitigate the potential for abuse.\u201d<\/p>\n

In a commentary to be published in Nature and timed with the publication of this study, policy analysts call for urgent regulation of this new technology. They highlight the many benefits of this work, but they also point out that \u201cindividuals with access to the yeast strain and basic skills in fermentation would be able to grow the yeast using the equivalent of a homebrew kit.\u201d<\/p>\n

They recommend restricting engineered yeast strains to licensed facilities and to authorized researchers, noting that it would be difficult to detect and control the illicit transport of such\u00a0strains.<\/p>\n

While such controls may help, Dueber said, \u201cAn additional concern is that once the knowledge of how to create an opiate-producing strain is out there, anyone trained in basic molecular biology could theoretically build it.\u201d<\/p>\n

Another target for regulation would be the companies that synthesize and sell DNA sequences. \u201cRestrictions are already in place for sequences tied to pathogenic organisms, like smallpox,\u201d said DeLoache. \u201cBut maybe it\u2019s time we also look at sequences for producing controlled substances.\u201d<\/p>\n

Other co-authors on this study are Zachary Russ and Andrew Gonzales of UC Berkeley\u2019s Department of Bioengineering, and Lauren Narcross of Concordia University\u2019s Department of Biology.<\/p>\n","protected":false},"excerpt":{"rendered":"

Fans of homebrewed beer and backyard distilleries already know how to employ yeast to convert sugar into alcohol. But a research team led by UC Berkeley bioengineers has gone much further by completing key steps needed to turn sugar-fed yeast into a microbial factory for producing morphine and potentially other drugs, including antibiotics and anti-cancer […]<\/p>\n","protected":false},"author":59,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_seopress_robots_primary_cat":"","nova_meta_subtitle":"","footnotes":""},"categories":[5572],"tags":[],"supplier":[5204,9936,22751],"class_list":["post-26160","post","type-post","status-publish","format-standard","hentry","category-bio-based","supplier-concordia-university","supplier-nature-chemical-biology","supplier-university-of-california-berkeley-uc-berkeley"],"_links":{"self":[{"href":"https:\/\/renewable-carbon.eu\/news\/wp-json\/wp\/v2\/posts\/26160","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/renewable-carbon.eu\/news\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/renewable-carbon.eu\/news\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/renewable-carbon.eu\/news\/wp-json\/wp\/v2\/users\/59"}],"replies":[{"embeddable":true,"href":"https:\/\/renewable-carbon.eu\/news\/wp-json\/wp\/v2\/comments?post=26160"}],"version-history":[{"count":0,"href":"https:\/\/renewable-carbon.eu\/news\/wp-json\/wp\/v2\/posts\/26160\/revisions"}],"wp:attachment":[{"href":"https:\/\/renewable-carbon.eu\/news\/wp-json\/wp\/v2\/media?parent=26160"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/renewable-carbon.eu\/news\/wp-json\/wp\/v2\/categories?post=26160"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/renewable-carbon.eu\/news\/wp-json\/wp\/v2\/tags?post=26160"},{"taxonomy":"supplier","embeddable":true,"href":"https:\/\/renewable-carbon.eu\/news\/wp-json\/wp\/v2\/supplier?post=26160"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}