Dissecting modular synthases through inhibition: A complementary chemical and genetic approach

[Display omitted] Modular synthases, such as fatty acid, polyketide, and non-ribosomal peptide synthases (NRPSs), are sophisticated machineries essential in both primary and secondary metabolism. Various techniques have been developed to understand their genetic background and enzymatic abilities. H...

Celý popis

Uložené v:
Podrobná bibliografia
Vydané v:Bioorganic & medicinal chemistry letters Ročník 30; číslo 2; s. 126820
Hlavní autori: Vickery, Christopher R., McCulloch, Ian P., Sonnenschein, Eva C., Beld, Joris, Noel, Joseph P., Burkart, Michael D.
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: England Elsevier Ltd 15.01.2020
Predmet:
Bacterial Proteins - metabolism
BpsA
Domain-specific inhibitors
Indigoidine
Natural products
Non-ribosomal peptide synthetase
Peptide Synthases - chemistry
Transferases (Other Substituted Phosphate Groups) - metabolism
Domain-specific inhibitors
BpsA
Non-ribosomal peptide synthetase
Natural products
Indigoidine
ISSN:0960-894X, 1464-3405, 1464-3405
On-line prístup:Získať plný text
Tagy: Pridať tag
Žiadne tagy, Buďte prvý, kto otaguje tento záznam!
Popis
Shrnutí:[Display omitted] Modular synthases, such as fatty acid, polyketide, and non-ribosomal peptide synthases (NRPSs), are sophisticated machineries essential in both primary and secondary metabolism. Various techniques have been developed to understand their genetic background and enzymatic abilities. However, uncovering the actual biosynthetic pathways remains challenging. Herein, we demonstrate a pipeline to study an assembly line synthase by interrogating the enzymatic function of each individual enzymatic domain of BpsA, a NRPS that produces the blue 3,3′-bipyridyl pigment indigoidine. Specific inhibitors for each biosynthetic domain of BpsA were obtained or synthesized, and the enzymatic performance of BpsA upon addition of each inhibitor was monitored by pigment development in vitro and in living bacteria. The results were verified using genetic mutants to inactivate each domain. Finally, the results complemented the currently proposed biosynthetic pathway of BpsA.
Bibliografia:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0960-894X
1464-3405
1464-3405
DOI:10.1016/j.bmcl.2019.126820