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Reprogramming the Biosynthesis of Cyclodepsipeptide Synthetases to Obtain New Enniatins and Beauvericins
- Source :
- ChemBioChem. 17:283-287
- Publication Year :
- 2016
- Publisher :
- Wiley, 2016.
-
Abstract
- Non-ribosomal peptide synthetases are complex multimodular biosynthetic machines that assemble various important and medically relevant peptide antibiotics. An interesting subgroup comprises the cyclodepsipeptide synthetases from fungi synthesizing cyclohexa- and cyclo-octadepsipeptides with antibacterial, anthelmintic, insecticidal, and anticancer properties; some are marketed drugs. We exploit the modularity of these highly homologous synthetases by fusing the hydroxy-acid-activating module of PF1022 synthetase with the amino-acid-activating modules of enniatin and beauvericin synthetase, thus yielding novel hybrid synthetases. The artificial synthetases expressed in Escherichia coli and the fungus Aspergillus niger yielded new cyclodepsipeptides, thus paving the way for the exploration of these derivatives for their bioactivity.
- Subjects :
- Dirofilaria immitis
Recombinant Fusion Proteins
Peptide
010402 general chemistry
medicine.disease_cause
01 natural sciences
Biochemistry
Substrate Specificity
Peptide Synthases
Industrial Microbiology
chemistry.chemical_compound
Biosynthesis
Depsipeptides
Escherichia coli
medicine
Animals
Humans
Cloning, Molecular
Molecular Biology
Anthelmintics
chemistry.chemical_classification
Depsipeptide
biology
010405 organic chemistry
Organic Chemistry
Aspergillus niger
Fungi
Protein engineering
biology.organism_classification
0104 chemical sciences
chemistry
Molecular Medicine
Dirofilariasis
Enniatin
Subjects
Details
- ISSN :
- 14394227
- Volume :
- 17
- Database :
- OpenAIRE
- Journal :
- ChemBioChem
- Accession number :
- edsair.doi.dedup.....c698d893af198bdec785016a4a92ca27