Adaptation of an L-Proline Adenylation Domain to Use 4-Propyl-L-Proline in the Evolution of Lincosamide Biosynthesis

Kadlčík, Stanislav; Kučera, Tomáš; Chalupská, Dominika; Gažák, Radek; Koběrská, Markéta; Ulanová, Dana; Kopecký, Jan; Kutejová, Eva; Najmanová, Lucie; Janata, Jiří

doi:https://dx.doi.org/10.1371/journal.pone.0084902

Number of the records: 1

Adaptation of an L-Proline Adenylation Domain to Use 4-Propyl-L-Proline in the Evolution of Lincosamide Biosynthesis

1.

SYSNO ASEP	0425633
Document Type	J - Journal Article
R&D Document Type	Journal Article
Subsidiary J	Článek ve WOS
Title	Adaptation of an L-Proline Adenylation Domain to Use 4-Propyl-L-Proline in the Evolution of Lincosamide Biosynthesis
Author(s)	Kadlčík, Stanislav (MBU-M)_{RID, ORCID} Kučera, Tomáš (MBU-M) Chalupská, Dominika (MBU-M) Gažák, Radek (MBU-M)_{RID, ORCID} Koběrská, Markéta (MBU-M)_ORCID Ulanová, Dana (MBU-M) Kopecký, Jan (MBU-M) Kutejová, Eva (MBU-M)_RID Najmanová, Lucie (MBU-M)_RID Janata, Jiří (MBU-M)_{RID, ORCID}
Source Title	PLoS ONE. - : Public Library of Science - ISSN 1932-6203 Roč. 8, č. 12 (2013)
Number of pages	16 s.
Language	eng - English
Country	US - United States
Keywords	NONRIBOSOMAL PEPTIDE SYNTHETASES ; GENE-CLUSTER ; BIOCHEMICAL-CHARACTERIZATION
Subject RIV	EE - Microbiology, Virology
R&D Projects	EE2.3.20.0055 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
	EE2.3.30.0003 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
	ED1.1.00/02.0109 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
Institutional support	MBU-M - RVO:61388971
UT WOS	000329117900118
DOI	https://doi.org/10.1371/journal.pone.0084902
Annotation	Clinically used lincosamide antibiotic lincomycin incorporates in its structure 4-propyl-L-proline (PPL), an unusual amino acid, while celesticetin, a less efficient related compound, makes use of proteinogenic L-proline. Biochemical characterization, as well as phylogenetic analysis and homology modelling combined with the molecular dynamics simulation were employed for complex comparative analysis of the orthologous protein pair LmbC and CcbC from the biosynthesis of lincomycin and celesticetin, respectively. The analysis proved the compared proteins to be the standalone adenylation domains strictly preferring their own natural substrate, PPL or L-proline. The LmbC substrate binding pocket is adapted to accomodate a rare PPL precursor. When compared with L-proline specific ones, several large amino acid residues were replaced by smaller ones opening a channel which allowed the alkyl side chain of PPL to be accommodated. One of the most important differences, that of the residue corresponding to V306 in CcbC changing to G308 in LmbC, was investigated in vitro and in silico.
Workplace	Institute of Microbiology
Contact	Eliška Spurná, eliska.spurna@biomed.cas.cz, Tel.: 241 062 231
Year of Publishing	2014

Number of the records: 1