Počet záznamů: 1
Lincosamide Synthetase-A Unique Condensation System Combining Elements of Nonribosomal Peptide Synthetase and Mycothiol Metabolism
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SYSNO ASEP 0444501 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Lincosamide Synthetase-A Unique Condensation System Combining Elements of Nonribosomal Peptide Synthetase and Mycothiol Metabolism Tvůrce(i) Janata, Jiří (MBU-M) RID, ORCID
Kadlčík, Stanislav (MBU-M) RID, ORCID
Koběrská, Markéta (MBU-M) ORCID
Ulanová, Dana (MBU-M)
Kameník, Zdeněk (MBU-M) RID, ORCID
Novák, Petr (MBU-M) RID, ORCID
Kopecký, Jan (MBU-M)
Novotná, Jitka (MBU-M)
Radojevič, Bojana (MBU-M) RID
Plháčková, Kamila (MBU-M) RID
Gažák, Radek (MBU-M) RID, ORCID
Najmanová, Lucie (MBU-M) RIDZdroj.dok. PLoS ONE. - : Public Library of Science - ISSN 1932-6203
Roč. 10, č. 3 (2015)Poč.str. 24 s. Jazyk dok. eng - angličtina Země vyd. US - Spojené státy americké Klíč. slova BIOSYNTHETIC GENE-CLUSTER ; MOLECULAR-WEIGHT THIOL ; PHOSPHOPANTETHEINYL TRANSFERASE Vědní obor RIV EE - Mikrobiologie, virologie CEP EE2.3.20.0055 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy EE2.3.30.0003 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy Institucionální podpora MBU-M - RVO:61388971 UT WOS 000350688100052 DOI 10.1371/journal.pone.0118850 Anotace 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 the cooperation of the previously characterized NRPS A-domain LmbC with a holo-LmbN-CP in activation of a 4-propyl-L-proline precursor of lincomycin. This result completed the functional characterization of LS subunits resembling NRPS initiation module. Two of the four remaining putative LS subunits, LmbE/CcbE and LmbV/CcbV, exhibit low but significant homology to enzymes from the metabolism of mycothiol, the NRPS-independent system processing the amino sugar and amino acid units. The functions of particular LS subunits as well as cooperation of both NRPS-based and NRPS-independent LS blocks are discussed. The described condensing enzyme represents a unique hybrid system with overall composition quite dissimilar to any other known enzyme system. Pracoviště Mikrobiologický ústav Kontakt Eliška Spurná, eliska.spurna@biomed.cas.cz, Tel.: 241 062 231 Rok sběru 2016
Počet záznamů: 1