Abstract
Peptide synthetases involved in the nonribosomal synthesis of peptide secondary metabolites possess a highly conserved domain structure. The arrangement of these domains within the multifunctional enzymes determines the number and order of the amino acid constituents of the peptide product. A general approach has been developed for targeted substitution of amino acid-activating domains within the srfA operon, which encodes the protein templates for the synthesis of the lipopeptide antibiotic surfactin in Bacillus subtilis. Exchange of domain-coding regions of bacterial and fungal origin led to the construction of hybrid genes that encoded peptide synthetases with altered amino acid specificities and the production of peptides with modified amino acid sequences.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Aminoacylation
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Anti-Bacterial Agents / biosynthesis*
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Anti-Bacterial Agents / chemistry
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Anti-Bacterial Agents / pharmacology
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Bacillus / genetics
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Bacillus subtilis / genetics
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Bacterial Proteins / biosynthesis*
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Bacterial Proteins / chemistry
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Bacterial Proteins / pharmacology
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Base Sequence
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Cloning, Molecular
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Genes, Bacterial
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Genes, Fungal
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Hemolysis / drug effects
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Lipopeptides
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Mass Spectrometry
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Molecular Sequence Data
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Operon
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Penicillium chrysogenum / genetics
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Peptide Synthases / chemistry
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Peptide Synthases / genetics*
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Peptides, Cyclic*
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Protein Engineering*
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Recombinant Fusion Proteins / biosynthesis
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Recombinant Fusion Proteins / chemistry
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Recombinant Fusion Proteins / pharmacology
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Transformation, Bacterial
Substances
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Anti-Bacterial Agents
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Bacterial Proteins
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Lipopeptides
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Peptides, Cyclic
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Recombinant Fusion Proteins
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surfactin peptide
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Peptide Synthases
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surfactin synthetase