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Biosynthesis of the antibiotic nonribosomal peptide penicillin in baker’s yeast

Awan, Ali R.; Blount, Benjamin A.; Bell, David J.; Shaw, William M.; Ho, Jack C.H.; McKiernan, Robert M.; Ellis, Tom

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Authors

Ali R. Awan

David J. Bell

William M. Shaw

Jack C.H. Ho

Robert M. McKiernan

Tom Ellis



Abstract

© The Author(s) 2017. Fungi are a valuable source of enzymatic diversity and therapeutic natural products including antibiotics. Here we engineer the baker’s yeast Saccharomyces cerevisiae to produce and secrete the antibiotic penicillin, a beta-lactam nonribosomal peptide, by taking genes from a filamentous fungus and directing their efficient expression and subcellular localization. Using synthetic biology tools combined with long-read DNA sequencing, we optimize productivity by 50-fold to produce bioactive yields that allow spent S. cerevisiae growth media to have antibacterial action against Streptococcus bacteria. This work demonstrates that S. cerevisiae can be engineered to perform the complex biosynthesis of multicellular fungi, opening up the possibility of using yeast to accelerate rational engineering of nonribosomal peptide antibiotics.

Citation

Awan, A. R., Blount, B. A., Bell, D. J., Shaw, W. M., Ho, J. C., McKiernan, R. M., & Ellis, T. (2017). Biosynthesis of the antibiotic nonribosomal peptide penicillin in baker’s yeast. Nature Communications, 8, Article 15202. https://doi.org/10.1038/ncomms15202

Journal Article Type Article
Acceptance Date Mar 9, 2017
Online Publication Date May 4, 2017
Publication Date 2017-08
Deposit Date Jun 3, 2020
Publicly Available Date Mar 28, 2024
Journal Nature Communications
Electronic ISSN 2041-1723
Publisher Nature Publishing Group
Peer Reviewed Peer Reviewed
Volume 8
Article Number 15202
DOI https://doi.org/10.1038/ncomms15202
Public URL https://nottingham-repository.worktribe.com/output/4183537
Publisher URL https://www.nature.com/articles/ncomms15202

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