Structural highlights
Function
GRSB_ANEMI This protein is a multifunctional enzyme, able to activate and polymerize the amino acids Pro, Val, Orn and Leu. Activation sites for these AA consist of individual domains.
Publication Abstract from PubMed
Engineering of biosynthetic enzymes is increasingly employed to synthesize structural analogues of antibiotics. Of special interest are non-ribosomal peptide synthetases (NRPSs) responsible for production of important antimicrobial peptides. Here, directed evolution of an adenylation domain of a Pro-specific NRPS module completely switched substrate specificity to the non-standard amino acid piperazic acid (Piz) bearing a labile N-N bond. This success was achieved by UPLC-MS/MS based screening of small, rationally designed mutant libraries and can presumably be replicated with a larger number of substrates and NRPS modules. The evolved NRPS produces a Piz-derived gramicidin S analogue. Thus, we give new impetus to the too-early dismissed idea that widely accessible low-throughput methods can switch the specificity of NRPSs in a biosynthetically useful fashion.
Directed Evolution of Piperazic Acid Incorporation by a Nonribosomal Peptide Synthetase.,Stephan P, Langley C, Winkler D, Basquin J, Caputi L, O'Connor SE, Kries H Angew Chem Int Ed Engl. 2023 Jun 16:e202304843. doi: 10.1002/anie.202304843. PMID:37326625[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Stephan P, Langley C, Winkler D, Basquin J, Caputi L, O'Connor SE, Kries H. Directed Evolution of Piperazic Acid Incorporation by a Nonribosomal Peptide Synthetase. Angew Chem Int Ed Engl. 2023 Jun 16:e202304843. PMID:37326625 doi:10.1002/anie.202304843
