Opiates are commonly used painkillers that are prescribed for illnesses ranging from cancer to rheumatism and toothaches. They are typically extracted from plants, and more efficient production of opiate has been attempted. Biotechnology methods for poppy cultivation to increase yields have been studied extensively; however, complex and unknown mechanisms that regulate biosynthetic pathways might make it difficult to increase opiate yields.
Although there are several examples of successful chemical opiate synthesis, cost-effective methods have not been established because of the complex molecular structure of opiates. Alternatively, as a next generation strategy, complete biosynthesis of opiates via microbes has also attracted attention because it does not require specific substrates other than inexpensive carbon sources (for example, glucose or glycerol), and has potential for improvements in quality and quantity.
The complete biosynthesis of the opiate thebaine and opioid hydrocodone in yeast are the first examples of successful production from simple substrates. The yeast fermentation system is sophisticated; however, thebaine and hydrocodone yields are still limited in that system. Opiates such as morphine and codeine are mainly obtained by extraction from opium poppies.
Researchers demonstrate in the journal Nature Communications that Escherichia coli serves as an efficient, robust and flexible platform for total opiate synthesis.
Thebaine, the most important raw material in opioid preparations, is produced by stepwise culture of four engineered strains at yields of 2.1 mg l−1 from glycerol, corresponding to a 300-fold increase from recently developed yeast systems. This improvement is presumably due to strong activity of enzymes related to thebaine synthesis from (R)-reticuline in E. coli.
Furthermore, by adding two genes to the thebaine production system, authors demonstrate the biosynthesis of hydrocodone, a clinically important opioid.
Improvements in opiate production in this E. coli system represent a major step towards the development of alternative opiate production systems.