Redesign of substrate selection in glycopeptide antibiotic biosynthesis enables 
effective formation of alternate peptide backbones

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

doi:10.1021/acschembio.0c00435

Item

ITEM ACTIONSEXPORT

Add to Basket

Local TagsRelease HistoryDetailsSummary

Released

Journal Article

Redesign of substrate selection in glycopeptide antibiotic biosynthesis enables effective formation of alternate peptide backbones

MPS-Authors

/persons/resource/persons117971

Kittilä, Tiia
Department of Biomolecular Mechanisms, Max Planck Institute for Medical Research, Max Planck Society;

External Resource

https://pubs.acs.org/doi/pdf/10.1021/acschembio.0c00435
(Any fulltext)

https://pubs.acs.org/doi/10.1021/acschembio.0c00435
(Any fulltext)

https://pubs.acs.org/doi/10.1021/acschembio.0c00435#article_content-right
(Any fulltext)

Fulltext (restricted access)

There are currently no full texts shared for your IP range.

Fulltext (public)

There are no public fulltexts stored in PuRe

Supplementary Material (public)

There is no public supplementary material available

Citation

Kaniusaite, M., Kittilä, T., Goode, R. J. A., Schittenhelm, R. B., & Cryle, M. J. (2020). Redesign of substrate selection in glycopeptide antibiotic biosynthesis enables effective formation of alternate peptide backbones. ACS Chemical Biology, 15(9), 2444-2455. doi:10.1021/acschembio.0c00435.

Cite as: https://hdl.handle.net/21.11116/0000-0006-DF8E-0

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.