Journal
NATURE COMMUNICATIONS
Volume 8, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms15202
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Funding
- BBSRC [BB/K006290/1, BB/K019791/1]
- EPSRC [EP/L011573/1]
- BBSRC [BB/K019791/1, BB/K006290/1] Funding Source: UKRI
- EPSRC [EP/L011573/1] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/K019791/1, BB/K006290/1] Funding Source: researchfish
- Engineering and Physical Sciences Research Council [EP/L011573/1] Funding Source: researchfish
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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.
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