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

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Title: Biosynthesis of the antibiotic nonribosomal peptide penicillin in baker's yeast
Authors: Awan, AR
Blount, BA
Bell, DJ
Shaw, WM
Ho, JCH
McKiernan, RM
Ellis, T
Item Type: Journal Article
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.
Issue Date: 4-May-2017
Date of Acceptance: 9-Mar-2017
URI: http://hdl.handle.net/10044/1/48888
DOI: 10.1038/ncomms15202
ISSN: 2041-1723
Publisher: Nature Research
Start Page: 1
End Page: 8
Journal / Book Title: Nature Communications
Volume: 8
Issue: 1
Copyright Statement: © The Author(s) 2017. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Sponsor/Funder: Biotechnology and Biological Sciences Research Council (BBSRC)
Biotechnology and Biological Sciences Research Council (BBSRC)
Engineering & Physical Science Research Council (EPSRC)
Funder's Grant Number: BB/K006290/1
BB/K019791/1
EP/L011573/1
Keywords: Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
NATURAL-PRODUCTS
SYNTHETIC BIOLOGY
ENGINEERED YEAST
CHRYSOGENUM
PEROXISOMES
TOOLKIT
Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
NATURAL-PRODUCTS
SYNTHETIC BIOLOGY
ENGINEERED YEAST
CHRYSOGENUM
PEROXISOMES
TOOLKIT
Anti-Bacterial Agents
Fermentation
Genetic Engineering
Penicillin G
Penicillins
Peptide Biosynthesis, Nucleic Acid-Independent
Saccharomyces cerevisiae
Streptococcus
Streptococcus
Saccharomyces cerevisiae
Penicillins
Penicillin G
Anti-Bacterial Agents
Genetic Engineering
Fermentation
Peptide Biosynthesis, Nucleic Acid-Independent
Publication Status: Published online
Open Access location: https://www.nature.com/articles/ncomms15202
Article Number: 15202
Online Publication Date: 2017-05-04
Appears in Collections:Bioengineering
Department of Infectious Diseases
Faculty of Medicine
Faculty of Engineering