Redesign of Substrate Selection in Glycopeptide Antibiotic Biosynthesis Enables Effective Formation of Alternate Peptide Backbones

Milda Kaniusaite, Tiia Kittilä, Robert J. A. Goode, Ralf B. Schittenhelm, Max J. Cryle

Research output: Contribution to journalArticleResearchpeer-review

2 Citations (Scopus)

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 languageEnglish
Pages (from-to)2444-2455
Number of pages12
JournalACS Chemical Biology
Volume15
Issue number9
DOIs
Publication statusPublished - 18 Sep 2020

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