An Argonaute from Thermus parvatiensis exhibits endonuclease activity mediated by 5′ chemically modified DNA guides

Prokaryotic Argonaute (pAgo) nucleases with precise DNA cleavage activity show great potential for gene <sc>manipulation</sc>. Extensive biochemical studies have revealed that recognition of guides with different 5′ groups by Ago is important for biocatalysis. Here, we identified an Ago...

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Main Authors: Sun Yingying, Guo Xiang, Lu Hui, Chen Liuqing, Huang Fei, Liu Qian, Feng Yan
Format: Article
Language:English
Published: China Science Publishing & Media Ltd. 2022-05-01
Series:Acta Biochimica et Biophysica Sinica
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Online Access:https://www.sciengine.com/doi/10.3724/abbs.2022047
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author Sun Yingying
Guo Xiang
Lu Hui
Chen Liuqing
Huang Fei
Liu Qian
Feng Yan
author_facet Sun Yingying
Guo Xiang
Lu Hui
Chen Liuqing
Huang Fei
Liu Qian
Feng Yan
author_sort Sun Yingying
collection DOAJ
description Prokaryotic Argonaute (pAgo) nucleases with precise DNA cleavage activity show great potential for gene <sc>manipulation</sc>. Extensive biochemical studies have revealed that recognition of guides with different 5′ groups by Ago is important for biocatalysis. Here, we identified an Ago from the thermophilic Thermus parvatiensis (TpsAgo) and analyzed the regulatory effect of 5′-modified guides on TpsAgo cleavage activity. Recombinant TpsAgo cleaves single-stranded DNA and RNA targets at 65–90°C, which is mediated by a 5′ hydroxyl or phosphate DNA guide. Notably, TpsAgo can utilize various 5′-modified DNA guides for catalysis, including 5′-NH<sub>2</sub>C<sub>6</sub>, 5′-Biotin, 5′-FAM and 5′-SHC<sub>6</sub> guides. Moreover, TpsAgo performs programmable cleavage of double-stranded DNA at temperatures over 80°C and strongly tolerates NaCl concentrations up to 3.2 M. These results provide insight into the catalytic performance of Agos by guide regulation, which may facilitate their biotechnological applications.
format Article
id doaj-art-6897a281a5594f2a88623bdaff01c4b3
institution Kabale University
issn 1672-9145
language English
publishDate 2022-05-01
publisher China Science Publishing & Media Ltd.
record_format Article
series Acta Biochimica et Biophysica Sinica
spelling doaj-art-6897a281a5594f2a88623bdaff01c4b32025-08-20T03:54:01ZengChina Science Publishing & Media Ltd.Acta Biochimica et Biophysica Sinica1672-91452022-05-015468669510.3724/abbs.202204720d259ccAn Argonaute from Thermus parvatiensis exhibits endonuclease activity mediated by 5′ chemically modified DNA guidesSun Yingying0Guo Xiang1Lu Hui2Chen Liuqing3Huang Fei4Liu Qian5Feng Yan6["State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China"]["State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China"]["State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China"]["Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China"]["State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China"]["State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China"]["State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China"]Prokaryotic Argonaute (pAgo) nucleases with precise DNA cleavage activity show great potential for gene <sc>manipulation</sc>. Extensive biochemical studies have revealed that recognition of guides with different 5′ groups by Ago is important for biocatalysis. Here, we identified an Ago from the thermophilic Thermus parvatiensis (TpsAgo) and analyzed the regulatory effect of 5′-modified guides on TpsAgo cleavage activity. Recombinant TpsAgo cleaves single-stranded DNA and RNA targets at 65–90°C, which is mediated by a 5′ hydroxyl or phosphate DNA guide. Notably, TpsAgo can utilize various 5′-modified DNA guides for catalysis, including 5′-NH<sub>2</sub>C<sub>6</sub>, 5′-Biotin, 5′-FAM and 5′-SHC<sub>6</sub> guides. Moreover, TpsAgo performs programmable cleavage of double-stranded DNA at temperatures over 80°C and strongly tolerates NaCl concentrations up to 3.2 M. These results provide insight into the catalytic performance of Agos by guide regulation, which may facilitate their biotechnological applications.https://www.sciengine.com/doi/10.3724/abbs.2022047Argonaute<italic>Thermus parvatiensis</italic>endonuclease5′-modified guide
spellingShingle Sun Yingying
Guo Xiang
Lu Hui
Chen Liuqing
Huang Fei
Liu Qian
Feng Yan
An Argonaute from Thermus parvatiensis exhibits endonuclease activity mediated by 5′ chemically modified DNA guides
Acta Biochimica et Biophysica Sinica
Argonaute
<italic>Thermus parvatiensis</italic>
endonuclease
5′-modified guide
title An Argonaute from Thermus parvatiensis exhibits endonuclease activity mediated by 5′ chemically modified DNA guides
title_full An Argonaute from Thermus parvatiensis exhibits endonuclease activity mediated by 5′ chemically modified DNA guides
title_fullStr An Argonaute from Thermus parvatiensis exhibits endonuclease activity mediated by 5′ chemically modified DNA guides
title_full_unstemmed An Argonaute from Thermus parvatiensis exhibits endonuclease activity mediated by 5′ chemically modified DNA guides
title_short An Argonaute from Thermus parvatiensis exhibits endonuclease activity mediated by 5′ chemically modified DNA guides
title_sort argonaute from thermus parvatiensis exhibits endonuclease activity mediated by 5 chemically modified dna guides
topic Argonaute
<italic>Thermus parvatiensis</italic>
endonuclease
5′-modified guide
url https://www.sciengine.com/doi/10.3724/abbs.2022047
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