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A microbial biomanufacturing platform for natural and semisynthetic opioids
Kate Thodey1, Stephanie Galanie2, Christina D Smolke1
1Department of Bioengineering, Stanford University, Stanford, California, USA.
Nature Chemical Biology
|August 25, 2014
Summary
Scientists engineered baker's yeast to produce medically essential opiates, creating a sustainable alternative to poppy cultivation. This yeast biomanufacturing platform offers improved security and efficiency for opioid production.
Area of Science:
- Biotechnology
- Synthetic Biology
- Biochemistry
Background:
- Opiates are crucial medicines, but traditional opium poppy cultivation presents supply chain challenges.
- Developing alternative, secure production methods for opiates is a significant unmet need.
Purpose of the Study:
- To engineer baker's yeast Saccharomyces cerevisiae as a microbial factory for opiate biosynthesis.
- To establish a sustainable and secure biomanufacturing platform for valuable benzylisoquinoline alkaloid drugs.
Main Methods:
- Engineered yeast strains to express heterologous genes from Papaver somniferum and Pseudomonas putida M10.
- Optimized yeast strains for titer and specificity through gene copy number titration, cosubstrate supply enhancement, spatial engineering, and high-density fermentation.
Main Results:
- Successfully converted thebaine to codeine, morphine, hydromorphone, hydrocodone, and oxycodone in engineered yeast.
- Discovered a novel biosynthetic branch leading to neopine and neomorphine, impacting pathway flux.
- Achieved total opioid titers up to 131 mg/l through strain optimization and fermentation.
Conclusions:
- Demonstrated the potential of Saccharomyces cerevisiae as a viable host for microbial opiate production.
- This work represents a critical advancement towards the total biosynthesis of opiate drugs.
- The developed yeast biomanufacturing platform offers a sustainable and secure alternative for opioid supply.
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