Design of N -acyl homoserine lactonase with high substrate specificity by a rational approach

Verfasser / Beitragende:
[Hyun-Ho Kyeong, Jin-Hyun Kim, Hak-Sung Kim]
Ort, Verlag, Jahr:
2015
Enthalten in:
Applied Microbiology and Biotechnology, 99/11(2015-06-01), 4735-4742
Format:
Artikel (online)
ID: 605506329
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024 7 0 |a 10.1007/s00253-014-6304-4  |2 doi 
035 |a (NATIONALLICENCE)springer-10.1007/s00253-014-6304-4 
245 0 0 |a Design of N -acyl homoserine lactonase with high substrate specificity by a rational approach  |h [Elektronische Daten]  |c [Hyun-Ho Kyeong, Jin-Hyun Kim, Hak-Sung Kim] 
520 3 |a N-Acyl homoserine lactone (AHL) is a major quorum-sensing signaling molecule in many bacterial species. Quorum-quenching (QQ) enzymes, which degrade such signaling molecules, have attracted much attention as an approach to controlling and preventing bacterial virulence and pathogenesis. However, naturally occurring QQ enzymes show a broad substrate spectrum, raising the concern of unintentionally attenuating beneficial effects by symbiotic bacteria. Here we report the rational design of acyl homoserine lactonase with high substrate specificity. Through docking analysis, we identified three key residues which play a key role in the substrate preference of the enzyme. The key residues were changed in a way that increases hydrophobic contact with a substrate having a short acyl chain (C4-AHL) while generating steric clashes with that containing a long acyl chain (C12-AHL). The resulting mutants exhibited a significantly shifted preference toward a substrate with a short acyl chain. Molecular dynamics simulations suggested that the mutations affect the behavior of a flexible loop, allowing tighter binding of a substrate with a short acyl chain. 
540 |a Springer-Verlag Berlin Heidelberg, 2014 
690 7 |a Quorum quenching  |2 nationallicence 
690 7 |a Acyl homoserine lactonase  |2 nationallicence 
690 7 |a Substrate preference  |2 nationallicence 
690 7 |a Rational design  |2 nationallicence 
700 1 |a Kyeong  |D Hyun-Ho  |u Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 305-701, Daejeon, Korea  |4 aut 
700 1 |a Kim  |D Jin-Hyun  |u LG Household & Health Care Ltd., R&D Institute, 305-343, Daejeon, Korea  |4 aut 
700 1 |a Kim  |D Hak-Sung  |u Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 305-701, Daejeon, Korea  |4 aut 
773 0 |t Applied Microbiology and Biotechnology  |d Springer Berlin Heidelberg  |g 99/11(2015-06-01), 4735-4742  |x 0175-7598  |q 99:11<4735  |1 2015  |2 99  |o 253 
856 4 0 |u https://doi.org/10.1007/s00253-014-6304-4  |q text/html  |z Onlinezugriff via DOI 
898 |a BK010053  |b XK010053  |c XK010000 
900 7 |a Metadata rights reserved  |b Springer special CC-BY-NC licence  |2 nationallicence 
908 |D 1  |a research-article  |2 jats 
949 |B NATIONALLICENCE  |F NATIONALLICENCE  |b NL-springer 
950 |B NATIONALLICENCE  |P 856  |E 40  |u https://doi.org/10.1007/s00253-014-6304-4  |q text/html  |z Onlinezugriff via DOI 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Kyeong  |D Hyun-Ho  |u Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 305-701, Daejeon, Korea  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Kim  |D Jin-Hyun  |u LG Household & Health Care Ltd., R&D Institute, 305-343, Daejeon, Korea  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Kim  |D Hak-Sung  |u Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 305-701, Daejeon, Korea  |4 aut 
950 |B NATIONALLICENCE  |P 773  |E 0-  |t Applied Microbiology and Biotechnology  |d Springer Berlin Heidelberg  |g 99/11(2015-06-01), 4735-4742  |x 0175-7598  |q 99:11<4735  |1 2015  |2 99  |o 253