Reconstituting the complete biosynthesis of D-lysergic acid in yeast
Garrett Wong,
Li Rong Lim,
Yong Quan Tan,
Maybelle Kho Go,
David J. Bell,
Paul S. Freemont () and
Wen Shan Yew ()
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Garrett Wong: National University of Singapore
Li Rong Lim: National University of Singapore
Yong Quan Tan: National University of Singapore
Maybelle Kho Go: National University of Singapore
David J. Bell: Imperial College London
Paul S. Freemont: Imperial College London
Wen Shan Yew: National University of Singapore
Nature Communications, 2022, vol. 13, issue 1, 1-10
Abstract:
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−1 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.
Date: 2022
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28386-6
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DOI: 10.1038/s41467-022-28386-6
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