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

Ali R. Awan, Benjamin A. Blount, David J. Bell, William M. Shaw, Jack C.H. Ho, Robert M. McKiernan and Tom Ellis ()
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Ali R. Awan: Centre for Synthetic Biology and Innovation, Imperial College London
Benjamin A. Blount: Centre for Synthetic Biology and Innovation, Imperial College London
David J. Bell: Centre for Synthetic Biology and Innovation, Imperial College London
William M. Shaw: Centre for Synthetic Biology and Innovation, Imperial College London
Jack C.H. Ho: Centre for Synthetic Biology and Innovation, Imperial College London
Robert M. McKiernan: Centre for Synthetic Biology and Innovation, Imperial College London
Tom Ellis: Centre for Synthetic Biology and Innovation, Imperial College London

Nature Communications, 2017, vol. 8, issue 1, 1-8

Abstract: Abstract 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.

Date: 2017
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DOI: 10.1038/ncomms15202

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