TY - JOUR T1 - Biosynthesis of the Antibiotic Nonribosomal Peptide Penicillin in Baker’s Yeast JF - bioRxiv DO - 10.1101/075325 SP - 075325 AU - Ali R. Awan AU - Benjamin A. Blount AU - David J. Bell AU - Jack C. H. Ho AU - Robert M. McKiernan AU - Tom Ellis Y1 - 2016/01/01 UR - http://biorxiv.org/content/early/2016/09/15/075325.abstract N2 - Fungi are a valuable source of enzymatic diversity and therapeutic natural products including antibiotics. By taking genes from a filamentous fungus and directing their efficient expression and subcellular localisation, we here engineer the baker’s yeast Saccharomyces cerevisiae to produce and secrete the antibiotic penicillin, a beta-lactam nonribosomal peptide. Using synthetic biology tools combined with long-read DNA sequencing, we optimise 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. ER -