New strategy for peptide engineering

10-Dec-2012 - Germany

Scientists in Germany have engineered peptide domains with altered substrate specificities, which lead the way for designer templates to make new bioactive products.

The group have studied hormaomycin, a structurally unusual antibiotic peptide, which is biosynthesized by a bacterial nonribosomal peptide synthetase (NRPS). Analysing amino acid residues of hormaomycin had previously revealed that the NRPS adenylation (A) domains naturally recombine during evolution. This inspired the team to create A domains with altered substrates, which in turn has uncovered new information about the NRPS pathway and suggests new strategies in peptide engineering.

Biosynthetic megaenzymes, such as NRPS, are currently of biomedical interest, as they produce a large number of bioactive metabolites via an assembly mechanism, which shows potential for artificial engineering. Nonribosomal peptides have many clinical applications, including antibiotics, antitumour agents and antifungals.

A significant advantage of this evolution-based engineering is that it requires no insight into protein structures, so while not effective for all NRPS systems, the experimental ease of this method makes it a useful addition to engineering techniques.

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