May 18, 2015

expert reaction to study investigating opioid synthesis by an engineered yeast, and comment

The production of pharmaceutical compounds from microorganisms is potentially cheaper and more effective than current methods, but there are obstacles which need to be overcome. These include increasing yields of the product, and such a result for the production of opiods in yeast has been reported by scientists publishing in the journal Nature Chemical Biology.

Prof. Paul Freemont, Co-Director of the EPSRC Centre for Synthetic Biology and Innovation, and Co-Director of the UK Innovation and Knowledge Centre for Synthetic Biology (SynbiCITE), Imperial College London, said:

“This study represents a growing trend in the emerging field of synthetic biology, which aims to develop a framework for the systematic engineering of living systems for useful purposes based on our ability to read and write DNA. One major aim is to develop sustainable biomanufacturing processes such that complex natural products like morphine can be manufactured more efficiently, cheaply and safely. Such processes would also lead to the possibility of further development of more effective pain-killers.

“Although this study and others represent an important landmark in achieving this, it throws open the whole debate on how such biomanufacturing processes can be safely regulated and also the need to engage with a wide array of stakeholders. This is due in part to the drive in the synthetic biology field to make biotechnology more accessible to non-experts, which has led to the rapid growth of amateur biologists or DIY-bio enthusiasts. Synthetic biology has also captured the imagination of thousands of undergraduate students worldwide, who compete annually in the Internationally Genetically Engineered Machine competition or iGEM.  With the widespread availability of digital biotechnology it is possible that non-experts and less-trained researchers could replicate such experiments, although they are still quite technically demanding.

“It is important to note I think that information for the chemical synthesis of illegal drugs has been available on the web or in the literature for some time with easy to follow recipes that in some cases can be followed by non-experts.  For new biomanufacturing processes like those described in these publications, I can envisage a series of safety features that could be engineered into specific production strains that would prevent  their use outside of a controlled and regulated environment. I could also imagine new DNA watermarks that could be introduced into production strains that would immediately allow the identification of such strains. There are already existing regulatory barriers to obtaining the necessary pieces of synthetic DNA from DNA synthesis companies that would be required to construct such production strains.

“I welcome the commentary by Oye et al as it provides a framework to initiate a wide debate on how these new biomanufacuring applications can be safely regulated and utilised for the wider good.”

Prof. John Ward, Professor of Synthetic Biology for Bioprocessing, Department of Biochemical Engineering, UCL, said:

“The paper shows the development of better enzymes in yeast for a pathway to make Reticuline. The researchers modify a pathway so that it diverts L-tyrosine away from an unwanted route to melanin.

“Reticuline is present in opium poppies in the pathway that they use to make morphine but is about 8 biosynthetic steps away from morphine.  The ability to make reticuline in yeast means that many compounds with potentially beneficial properties could be made based on the reticuline molecule.”

Paper: ‘An enzyme-coupled biosensor enables (S)-reticuline production in yeast from glucose’ by William C DeLoache et al. published in Nature Chemical Biology on Monday 18 May 2015. 

Comment: ‘Regulate ‘home-brew’ opiates’ by Kenneth Oye et al. published in Nature on Monday 18 May 2015.

Declared interests

Prof. Paul Freemont: “I am employed by Imperial College London as a professor.  I hold grant funding from the major RCUK funding agencies including BBSRC, EPSRC, Innovate UK and also charity funding from CRUK and the CF Trust.  I am a board member of the MRC MCMB funding panel and recently chair of the Diamond Scientific Advisory Committee.  I am a Fellow of the Society of Biology and the Royal Society of Medicine.  I am Co-founder and Co-Director of the EPSRC Centre for Synthetic Biology and Innovation & the UK Innovation and Knowledge Centre for Synthetic Biology (SynbiCITE- Imperial College London, www.imperial.ac.uk/syntheticbiology, www.synbicite.com).  I am also head of the Section of Structural Biology in the Department of Medicine at Imperial College London.  I am co-founder and equity holder of two start companies – Equinox Pharma Ltd which specialises in computational drug discovery, and LabGenius Ltd which specialises in optimisation of industrial protein production. None of these companies have any interest in the biomanufacturing of pharmaceuticals or chemicals.”

Prof. John Ward: “I have received funding previously from the BBSRC to carry out research on an enzyme called norcoclaurine synthase which is in many plants which make compounds called benzyl isoquinolines (BIAs). Morphine and other compounds in the opium poppy are BIAs but there are about 12,000 other BIA alkaloids some of which have beneficial properties such as anticancer and antimicrobial compounds.”