RT Journal Article
SR Electronic
T1 Biosynthesis of the Antibiotic Nonribosomal Peptide Penicillin in Baker’s Yeast
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 075325
DO 10.1101/075325
A1 Ali R. Awan
A1 Benjamin A. Blount
A1 David J. Bell
A1 Jack C. H. Ho
A1 Robert M. McKiernan
A1 Tom Ellis
YR 2016
UL http://biorxiv.org/content/early/2016/09/15/075325.abstract
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.