Abstract
Nonribosomal peptide synthesis is capable of utilizing a wide range of amino acid residues due to the selectivity of adenylation (A)-domains. Changing the selectivity of A-domains could lead to new bioactive nonribosomal peptides, although remodeling efforts of A-domains are often unsuccessful. Here, we explored and successfully reengineered the specificity of the module 3 A-domain from glycopeptide antibiotic biosynthesis to change the incorporation of 3,5-dihydroxyphenylglycine into 4-hydroxyphenylglycine. These engineered A-domains remain selective in a functioning peptide assembly line even under substrate competition conditions and indicate a possible application of these for the future redesign of GPA biosynthesis.
Original language | English |
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Pages (from-to) | 2444-2455 |
Number of pages | 12 |
Journal | ACS Chemical Biology |
Volume | 15 |
Issue number | 9 |
DOIs | |
Publication status | Published - 18 Sep 2020 |
Equipment
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Monash Proteomics & Metabolomics Facility
Ralf Schittenhelm (Manager)
Office of the Vice-Provost (Research and Research Infrastructure)Facility/equipment: Facility