MIT Libraries logoDSpace@MIT

MIT
View Item 
  • DSpace@MIT Home
  • MIT Open Access Articles
  • MIT Open Access Articles
  • View Item
  • DSpace@MIT Home
  • MIT Open Access Articles
  • MIT Open Access Articles
  • View Item
JavaScript is disabled for your browser. Some features of this site may not work without it.

An Engineered Synthetic Pathway for Discovering Nonnatural Nonribosomal Peptides in Escherichia coli

Author(s)
Lu, Timothy K; Cleto, Sara
Thumbnail
DownloadmBio-2017-Cleto-.pdf (1.151Mb)
PUBLISHER_CC

Publisher with Creative Commons License

Creative Commons Attribution

Terms of use
Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/
Metadata
Show full item record
Abstract
Peptides that are synthesized independently of the ribosome in plants, fungi, and bacteria can have clinically relevant anticancer, antihemochromatosis, and antiviral activities, among many other. Despite their natural origin, discovering new natural products is challenging, and there is a need to expand the chemical diversity that is accessible. In this work, we created a novel, compressed synthetic pathway for the heterologous expression and diversification of nonribosomal peptides (NRPs) based on homologs of siderophore pathways from Escherichia coli and Vibrio cholerae. To enhance the likelihood of successful molecule production, we established a selective pressure via the iron-chelating properties of siderophores. By supplementing cells containing our synthetic pathway with different precursors that are incorporated into the pathway independently of NRP enzymes, we generated over 20 predesigned, novel, and structurally diverse NRPs. This engineering approach, where phylogenetically related genes from different organisms are integrated and supplemented with novel precursors, should enable heterologous expression and molecular diversification of NRPs.
Date issued
2017-10
URI
http://hdl.handle.net/1721.1/114599
Department
Massachusetts Institute of Technology. Department of Biological Engineering; Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science; Massachusetts Institute of Technology. Synthetic Biology Center
Journal
mBio
Publisher
American Society for Microbiology
Citation
Cleto, Sara, and Timothy K. Lu. “An Engineered Synthetic Pathway for Discovering Nonnatural Nonribosomal Peptides in Escherichia Coli.” MBio, edited by Julian E. Davies, vol. 8, no. 5, Nov. 2017, pp. e01474-17. © 2017 American Society for Microbiology
Version: Final published version
ISSN
2150-7511

Collections
  • MIT Open Access Articles

Browse

All of DSpaceCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsThis CollectionBy Issue DateAuthorsTitlesSubjects

My Account

Login

Statistics

OA StatisticsStatistics by CountryStatistics by Department
MIT Libraries
PrivacyPermissionsAccessibilityContact us
MIT
Content created by the MIT Libraries, CC BY-NC unless otherwise noted. Notify us about copyright concerns.