Farming opioids from sugar

Metabolic engineering of yeast cells to produce pharmaceutical and natural products has been around for some time, notably used for production of a precursor metabolite of the widely used antimalarial drug artemisinin. Galanie et al. [1] demonstrated that metabolic pathways from other organisms can be reconstructed in yeast to synthesize complex natural products such as opiates and their opioid derivatives. Opioids are widely used as painkillers and also have diverse effects on the human body. The authors engineered yeast strains to express and knockout more than 20 heterologous genes, from organisms like plants, rats, bacteria and even yeast to convert central metabolites to thebaine, a precursor for codeine – the most commonly used opiate. Biosynthetic production of natural products is tackled by modularizing the genetic circuits to produce intermediate metabolites. The authors (i) first created a module to produce (S)-reticuline from tyrosine; (ii) convert (S)-reticuline to (R)-reticuline, a key step in the pathway; (iii) optimized the conversion of (R)-reticuline to thebaine. Enhancing the production efficiency by diverting metabolic flux through the existing modules and additional pathway engineering could scale-up the process and make it possible for commercial production.

  1. Galanie S, Thodey K, Trenchard IJ, Filsinger Interrante M, Smolke CD. Complete biosynthesis of opioids in yeast. Science. 2015 Sep 4;349(6252):1095-100.

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