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Issue 3, 2013
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Evolution-guided engineering of nonribosomal peptide synthetase adenylation domains

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Abstract

Hormaomycin is a structurally unusual morphogenic and antibiotic peptide biosynthesized by a bacterial nonribosomal peptide synthetase (NRPS). Bioinformatic analysis suggested that parts of the NRPS adenylation (A) domains had recombined during evolution, resulting in a major switch of substrate specificity. This feature inspired us to create A domains with altered substrates based on the putative recombination points. Following characterization of all native hormaomycin A domains, engineered versions were constructed and characterized. Three of the enzymes displayed an almost identical specificity profile to that of native domains recognizing the same substrates. The data support the evolutionary hypothesis regarding the emergence of the hormaomycin pathway and suggest new strategies in NRPS engineering.

Graphical abstract: Evolution-guided engineering of nonribosomal peptide synthetase adenylation domains

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Supplementary files

Article information


Submitted
10 Oct 2012
Accepted
26 Nov 2012
First published
26 Nov 2012

Chem. Sci., 2013,4, 1041-1045
Article type
Edge Article

Evolution-guided engineering of nonribosomal peptide synthetase adenylation domains

M. Crüsemann, C. Kohlhaas and J. Piel, Chem. Sci., 2013, 4, 1041
DOI: 10.1039/C2SC21722H

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