An engineered synthetic pathway for discovering non-natural nonribosomal peptides in E. coli
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Peptides that are synthesized
independently of the ribosome in plants, fungi, and bacteria can have clinically
relevant anti-cancer, anti-hemochromatosis,
and anti-viral activities, among many others. 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 twenty
pre-designed, 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.
COLLECTION SIZE
11.23 MB
CATEGORIES
- Bacteriology
- Agricultural biotechnology not elsewhere classified
- Bioinformatic methods development
- Bioinformatics and computational biology not elsewhere classified
- Other biological sciences not elsewhere classified
- Medical biotechnology not elsewhere classified
- Microbial genetics
- Microbiology not elsewhere classified
- Plant cell and molecular biology
- Animal cell and molecular biology
- Synthetic biology