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.  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.
- 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.
The dreadful effects of malaria need no recalling. One strategy to counter it is by creating mutant mosquitoes that are resistant to the parasites. However, the bottleneck has always been to ensure that the mutant mosquitoes should also spread in the wild population rapidly. Gantz et. al.  exploited the genome editing power of CRISPR to create a method for mutagenic chain reaction (MCR)  in mosquitoes. MCR technology allows us to create homozygous loss-of-function mutations in the germ line of the host organism that spreads rapidly through its offspring. Inserting mutations in two genes that cause resistance to the malarial parasite, the authors engineered a gene drive that passed on the modified homozygous genes to 99% of their offspring. Gene drives based on CRISPR-Cas9 have the potential to rapidly spread through the wild population. However, a lot of work is still required to assess its stability when introduced in a gene pool and developing human regulatory control before the powerful technology can be taken out of the lab.
- Gantz VM, Jasinskiene N, Tatarenkova O, Fazekas A, Macias VM, Bier E, James AA. Highly efficient Cas9-mediated gene drive for population modification of the malaria vector mosquito Anopheles stephensi. Proc Natl Acad Sci U S A. 2015 Dec 8; 112(49):E6736-43.
- Gantz VM, Bier E. Genome editing. The mutagenic chain reaction: a method for converting heterozygous to homozygous mutations. Science. 2015 Apr 24;348(6233):442-4.