N-Deacetylation in Lincosamide Biosynthesis Is Catalyzed by a TIdD/PmbA Family Protein

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388971%3A_____%2F20%3A00533399" target="_blank" >RIV/61388971:_____/20:00533399 - isvavai.cz</a>

Výsledek na webu

<a href="https://pubs.acs.org/doi/abs/10.1021/acschembio.0c00224" target="_blank" >https://pubs.acs.org/doi/abs/10.1021/acschembio.0c00224</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acschembio.0c00224" target="_blank" >10.1021/acschembio.0c00224</a>

Jazyk výsledku

angličtina

Název v původním jazyce

N-Deacetylation in Lincosamide Biosynthesis Is Catalyzed by a TIdD/PmbA Family Protein

Popis výsledku v původním jazyce

Lincosamides are clinically important antibiotics originally produced as microbial specialized metabolites. The complex biosynthesis of lincosamides is coupled to the metabolism of mycothiol as a sulfur donor. Here, we elucidated the N-deacetylation of the mycothiol-derived N-acetyl-L-cysteine residue of a lincosamide intermediate, which is comprised of an amino acid and an aminooctose connected via an amide bond. We purified this intermediate from the culture broth of a deletion mutant strain and tested it as a substrate of recombinant lincosamide biosynthetic proteins in the in vitro assays that were monitored via liquid chromatography-mass spectrometry. Our findings showed that the N-deacetylation reaction is catalyzed by CcbIH/CcbQ or LmbIH/LmbQ proteins in celesticetin and lincomycin biosynthesis, respectively. These are the first N-deacetylases from the TIdD/PmbA protein family, from which otherwise only several proteases and peptidases were functionally characterized. Furthermore, we present a sequence similarity network of TldD/PmbA proteins, which suggests that the lincosamide N-deacetylases are unique among these widely distributed proteins.

Název v anglickém jazyce

N-Deacetylation in Lincosamide Biosynthesis Is Catalyzed by a TIdD/PmbA Family Protein

Popis výsledku anglicky

Lincosamides are clinically important antibiotics originally produced as microbial specialized metabolites. The complex biosynthesis of lincosamides is coupled to the metabolism of mycothiol as a sulfur donor. Here, we elucidated the N-deacetylation of the mycothiol-derived N-acetyl-L-cysteine residue of a lincosamide intermediate, which is comprised of an amino acid and an aminooctose connected via an amide bond. We purified this intermediate from the culture broth of a deletion mutant strain and tested it as a substrate of recombinant lincosamide biosynthetic proteins in the in vitro assays that were monitored via liquid chromatography-mass spectrometry. Our findings showed that the N-deacetylation reaction is catalyzed by CcbIH/CcbQ or LmbIH/LmbQ proteins in celesticetin and lincomycin biosynthesis, respectively. These are the first N-deacetylases from the TIdD/PmbA protein family, from which otherwise only several proteases and peptidases were functionally characterized. Furthermore, we present a sequence similarity network of TldD/PmbA proteins, which suggests that the lincosamide N-deacetylases are unique among these widely distributed proteins.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10606 - Microbiology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2020

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

ACS Chemical Biology

ISSN

1554-8929

e-ISSN

1554-8937

Svazek periodika

15

Číslo periodika v rámci svazku

8

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

7

Strana od-do

2048-2054

Kód UT WoS článku

000563743000004

EID výsledku v databázi Scopus

2-s2.0-85089786972