PT  - JOURNAL ARTICLE
AU  - Ali R. Awan
AU  - Benjamin A. Blount
AU  - David J. Bell
AU  - Jack C. H. Ho
AU  - Robert M. McKiernan
AU  - Tom Ellis
TI  - Biosynthesis of the Antibiotic Nonribosomal Peptide Penicillin in Baker’s Yeast
AID  - 10.1101/075325
DP  - 2016 Jan 01
TA  - bioRxiv
PG  - 075325
4099  - http://biorxiv.org/content/early/2016/09/15/075325.short
4100  - http://biorxiv.org/content/early/2016/09/15/075325.full
AB  - 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.