AI Article Synopsis
- Ergot alkaloids are natural compounds used to treat neurological conditions like Parkinsonism and dementia, and their complex synthesis poses challenges.
- Current chemical synthesis is lengthy and not selective, while biological methods with ergot fungi can yield unwanted products and degrade over time.
- This research shows a successful production of D-lysergic acid, a key precursor for ergot alkaloids, using engineered yeast in a bioreactor, offering a potential solution for more effective production methods.
Article Abstract
The ergot alkaloids are a class of natural products known for their pharmacologically privileged molecular structure that are used in the treatment of neurological ailments, such as Parkinsonism and dementia. Their synthesis via chemical and biological routes are therefore of industrial relevance, but suffer from several challenges. Current chemical synthesis methods involve long, multi-step reactions with harsh conditions and are not enantioselective; biological methods utilizing ergot fungi, produce an assortment of products that complicate product recovery, and are susceptible to strain degradation. Reconstituting the ergot alkaloid pathway in a strain strongly amenable for liquid fermentation, could potentially resolve these issues. In this work, we report the production of the main ergoline therapeutic precursor, D-lysergic acid, to a titre of 1.7 mg L in a 1 L bioreactor. Our work demonstrates the proof-of-concept for the biological production of ergoline-derived compounds from sugar in an engineered yeast chassis.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8821704 | PMC |
| http://dx.doi.org/10.1038/s41467-022-28386-6 | DOI Listing |
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