Lincosamide synthetase--a unique condensation system combining elements of nonribosomal peptide synthetase and mycothiol metabolism

PloS One
Jirí JanataLucie Najmanová

Abstract

In the biosynthesis of lincosamide antibiotics lincomycin and celesticetin, the amino acid and amino sugar units are linked by an amide bond. The respective condensing enzyme lincosamide synthetase (LS) is expected to be an unusual system combining nonribosomal peptide synthetase (NRPS) components with so far unknown amino sugar related activities. The biosynthetic gene cluster of celesticetin was sequenced and compared to the lincomycin one revealing putative LS coding ORFs shared in both clusters. Based on a bioassay and production profiles of S. lincolnensis strains with individually deleted putative LS coding genes, the proteins LmbC, D, E, F and V were assigned to LS function. Moreover, the newly recognized N-terminal domain of LmbN (LmbN-CP) was also assigned to LS as a NRPS carrier protein (CP). Surprisingly, the homologous CP coding sequence in celesticetin cluster is part of ccbZ gene adjacent to ccbN, the counterpart of lmbN, suggesting the gene rearrangement, evident also from still active internal translation start in lmbN, and indicating the direction of lincosamide biosynthesis evolution. The in vitro test with LmbN-CP, LmbC and the newly identified S. lincolnensis phosphopantetheinyl transferase Slp, confirmed th...Continue Reading

References

Nov 1, 1996·Chemistry & Biology·R H LambalotC T Walsh
Aug 26, 1998·The Journal of Biological Chemistry·T StachelhausM A Marahiel
Aug 17, 2002·Science·Joachim AhlertJon S Thorson
Feb 4, 2003·Proceedings of the National Academy of Sciences of the United States of America·Bertolt GustKeith F Chater
Mar 10, 2004·Applied and Environmental Microbiology·Daisuke IshiyamaJulian Davies
Sep 10, 2004·European Journal of Biochemistry·Jitka NovotnáJaroslav Spízek
Jan 6, 2005·The Journal of Biological Chemistry·Hee-Jeon HongMark J Buttner
Jun 23, 2007·Chemistry & Biology·Yunfeng HuBrian O Bachmann
Jun 24, 2008·Archives of Microbiology·Volker DangelLutz Heide
Sep 6, 2008·Microbiology and Molecular Biology Reviews : MMBR·Gerald L NewtonRobert C Fahey
Nov 26, 2008·Natural Product Reports·Vishnu Karthik Jothivasan, Chris J Hamilton
Mar 10, 2009·Applied and Environmental Microbiology·Wei LiBarbara Gerratana
Mar 10, 2009·Applied and Environmental Microbiology·Wei LiBarbara Gerratana
Apr 21, 2009·Methods in Enzymology·Barrie Wilkinson, Jason Micklefield
Nov 18, 2009·Antimicrobial Agents and Chemotherapy·Dana UlanovaJirí Janata
Mar 24, 2010·Proceedings of the National Academy of Sciences of the United States of America·Ahmed GaballaJohn D Helmann
Nov 27, 2010·Nucleic Acids Research·Aron Marchler-BauerStephen H Bryant
Feb 7, 2012·Physical Chemistry Chemical Physics : PCCP·Silvia FerrerJuan Bertrán
Jul 24, 2012·Nature Chemical Biology·Chitose MaruyamaYoshimitsu Hamano

❮ Previous
Next ❯

Citations

Dec 13, 2016·Biochemical Pharmacology·Jaroslav Spížek, Tomáš Řezanka
Apr 19, 2017·Chemical Reviews·Kyle L DunbarChristian Hertweck
Jul 20, 2016·Chembiochem : a European Journal of Chemical Biology·Richiro UshimaruHung-Wen Liu
Apr 30, 2017·Applied Microbiology and Biotechnology·Sitong MengLinquan Bai
Mar 27, 2018·Journal of Industrial Microbiology & Biotechnology·Yurong XuBuchang Zhang
Mar 17, 2021·Journal of Histotechnology·Mehri MirhoseiniFereshteh Talebpour Amiri
Aug 14, 2020·ACS Chemical Biology·Simon VobrubaJiri Janata

❮ Previous
Next ❯

Datasets Mentioned

BETA
KM252689

Methods Mentioned

BETA
PCR
aminoacylation

Software Mentioned

BLAST
DataAnalysis
Hystar
ftmsControl
BLASTP
BLASTX

Related Concepts

Related Feeds

Antifungals (ASM)

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.

Antifungals

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.