Journal
CHEMBIOCHEM
Volume 17, Issue 4, Pages 283-287Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cbic.201500649
Keywords
biosynthesis; cyclodepsipeptides; enniatin; module exchange; non-ribosomal peptide synthetase; protein engineering
Funding
- Cluster of Excellence - German Research Council (DFG)
- Marie Curie Initial Training Network QuantFung [607332]
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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.
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