Many drugs are still produced the traditional way, by extraction from medicinal plants. In the Smolke laboratory we are working to take a drug biosynthetic pathway from a medicinal crop – the opium poppy – and engineer the production of the same therapeutic molecules in an industrial microbe, yeast.
As a Postdoc working together with members of the Metabolic Engineering team, my research focuses broadly on metabolically-engineering yeast to produce opiate alkaloids such as morphine and codeine. In order to maximize the number and quantity of morphinan alkaloids we can produce by microbial fermentation, my approach is to focus on the spatial engineering of this pathway in the host yeast cell. Spatial engineering is particularly useful in this instance because in the natural system, the opium poppy, the biosynthesis of opiates takes place across several cell types and subcellular structures. It could therefore be expected that efforts to engineer this pathway within single-celled yeast would benefit from making use of the available cellular compartments. Yeast organelles could provide microenvironments that are conducive to opiate alkaloid biosynthesis due to optimal pH or the availability of cofactors; they could compartmentalize toxic metabolites or ensure a local concentration of reactive intermediates; and they may be used to support the reconstitution of enzyme complexes which form naturally in the opium poppy. In the future, we envisage that the development of yeast synthetic organelles could support further spatial engineering efforts without taxing the functioning of native organelles.
biosynthesis in yeast with synthetic biology tools. FEMS Yeast Res. 2012 Mar;12(2):144-70. doi: 10.1111/j.1567-1364.2011.00774.x. Epub 2012 Jan 11. PubMed PMID: 22136110.
genetically-encoded biosensors for the construction and control of biosynthetic pathways. Metab Eng. 2011 Sep 18. [Epub ahead of print] PubMed PMID: 21946159; PubMed Central PMCID: PMC3256257.
2011 Jul 22;333(6041):412-3. PubMed PMID: 21778388.