Directed Evolution Reveals the Functional Sequence Space of an Adenylation Domain Specificity Code.


Journal

ACS chemical biology
ISSN: 1554-8937
Titre abrégé: ACS Chem Biol
Pays: United States
ID NLM: 101282906

Informations de publication

Date de publication:
20 09 2019
Historique:
pubmed: 21 8 2019
medline: 9 4 2020
entrez: 21 8 2019
Statut: ppublish

Résumé

Nonribosomal peptides are important natural products biosynthesized by nonribosomal peptide synthetases (NRPSs). Adenylation (A) domains of NRPSs are highly specific for the substrate they recognize. This recognition is determined by 10 residues in the substrate-binding pocket, termed the specificity code. This finding led to the proposal that nonribosomal peptides could be altered by specificity code swapping. Unfortunately, this approach has proven, with few exceptions, to be unproductive; changing the specificity code typically results in broadened specificity or poor function. To enhance our understanding of A domain substrate selectivity, we carried out a detailed analysis of the specificity code from the A domain of EntF, an NRPS involved in enterobactin biosynthesis in

Identifiants

pubmed: 31430120
doi: 10.1021/acschembio.9b00532
pmc: PMC6800085
mid: NIHMS1053722
doi:

Substances chimiques

Ethylenediamines 0
Iron Chelating Agents 0
ethylenediamine-N,N'-bis(2-hydroxyphenylacetic acid) 1170-02-1
Serine 452VLY9402
Peptide Synthases EC 6.3.2.-
2,3-dihydroxybenzoate - serine ligase EC 6.3.2.14

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

2044-2054

Subventions

Organisme : NIGMS NIH HHS
ID : R01 GM100346
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM008349
Pays : United States

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Auteurs

Kurt Throckmorton (K)

Department of Bacteriology , University of Wisconsin-Madison , Madison , Wisconsin 53706 , United States.

Vladimir Vinnik (V)

Department of Bacteriology , University of Wisconsin-Madison , Madison , Wisconsin 53706 , United States.

Ratul Chowdhury (R)

Department of Chemical Engineering , The Pennsylvania State University , University Park , Pennsylvania 16802 , United States.

Taylor Cook (T)

Department of Chemical and Biological Engineering , University of Wisconsin-Madison , Madison , Wisconsin 53706 , United States.

Marc G Chevrette (MG)

Department of Bacteriology , University of Wisconsin-Madison , Madison , Wisconsin 53706 , United States.
Department of Genetics , University of Wisconsin-Madison , Madison , Wisconsin 53706 , United States.

Costas Maranas (C)

Department of Chemical Engineering , The Pennsylvania State University , University Park , Pennsylvania 16802 , United States.

Brian Pfleger (B)

Department of Chemical and Biological Engineering , University of Wisconsin-Madison , Madison , Wisconsin 53706 , United States.

Michael George Thomas (MG)

Department of Bacteriology , University of Wisconsin-Madison , Madison , Wisconsin 53706 , United States.

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Classifications MeSH