Fast and precise multi-site mutagenesis on linear DNA fragments

The effectiveness and scalability of site-directed mutagenesis are constrained by the limited number of mutations and the intricate cloning process required for isolation of the target sequence. Here, we present a method for precise introduction of multiple non-contiguous mutations. The mutant stran...

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Main Authors: Jie Zhang, Youhui Yang, Zhaoguan Wang, Qian Liu, Peixian Li, Shaohua Kang, Hao Qi
Format: Article
Language:English
Published: Taylor & Francis Group 2024-12-01
Series:Biotechnology & Biotechnological Equipment
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Online Access:https://www.tandfonline.com/doi/10.1080/13102818.2024.2385423
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author Jie Zhang
Youhui Yang
Zhaoguan Wang
Qian Liu
Peixian Li
Shaohua Kang
Hao Qi
author_facet Jie Zhang
Youhui Yang
Zhaoguan Wang
Qian Liu
Peixian Li
Shaohua Kang
Hao Qi
author_sort Jie Zhang
collection DOAJ
description The effectiveness and scalability of site-directed mutagenesis are constrained by the limited number of mutations and the intricate cloning process required for isolation of the target sequence. Here, we present a method for precise introduction of multiple non-contiguous mutations. The mutant strands are collected through one specially designed magnetic bead separation in alkaline conditions, efficiently removing their complementary partner strands with the original sequences. In a proof-of-concept test, a green fluorescent protein (GFP) was simultaneously mutated in 1–3 specific amino acids, successfully shifting its fluorescence spectrum. The precise mutation rates for single-, double- and triple-site mutations reached 100%, 76% and 70%, respectively. This multiple non-contiguous mutagenesis method may offer a fast and cost-effective approach for customizable construction of gene library.
format Article
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institution OA Journals
issn 1310-2818
1314-3530
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publishDate 2024-12-01
publisher Taylor & Francis Group
record_format Article
series Biotechnology & Biotechnological Equipment
spelling doaj-art-fbaf98adaeb846c28db79cd49962d4432025-08-20T01:59:17ZengTaylor & Francis GroupBiotechnology & Biotechnological Equipment1310-28181314-35302024-12-0138110.1080/13102818.2024.2385423Fast and precise multi-site mutagenesis on linear DNA fragmentsJie Zhang0Youhui Yang1Zhaoguan Wang2Qian Liu3Peixian Li4Shaohua Kang5Hao Qi6Department of Pharmaceutical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin, PR ChinaDepartment of Pharmaceutical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin, PR ChinaDepartment of Pharmaceutical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin, PR ChinaDepartment of Pharmaceutical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin, PR ChinaDepartment of Pharmaceutical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin, PR ChinaDepartment of Pharmaceutical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin, PR ChinaDepartment of Pharmaceutical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin, PR ChinaThe effectiveness and scalability of site-directed mutagenesis are constrained by the limited number of mutations and the intricate cloning process required for isolation of the target sequence. Here, we present a method for precise introduction of multiple non-contiguous mutations. The mutant strands are collected through one specially designed magnetic bead separation in alkaline conditions, efficiently removing their complementary partner strands with the original sequences. In a proof-of-concept test, a green fluorescent protein (GFP) was simultaneously mutated in 1–3 specific amino acids, successfully shifting its fluorescence spectrum. The precise mutation rates for single-, double- and triple-site mutations reached 100%, 76% and 70%, respectively. This multiple non-contiguous mutagenesis method may offer a fast and cost-effective approach for customizable construction of gene library.https://www.tandfonline.com/doi/10.1080/13102818.2024.2385423Multisite mutagenesisalkaline denaturationsingle-stranded DNAGFP
spellingShingle Jie Zhang
Youhui Yang
Zhaoguan Wang
Qian Liu
Peixian Li
Shaohua Kang
Hao Qi
Fast and precise multi-site mutagenesis on linear DNA fragments
Biotechnology & Biotechnological Equipment
Multisite mutagenesis
alkaline denaturation
single-stranded DNA
GFP
title Fast and precise multi-site mutagenesis on linear DNA fragments
title_full Fast and precise multi-site mutagenesis on linear DNA fragments
title_fullStr Fast and precise multi-site mutagenesis on linear DNA fragments
title_full_unstemmed Fast and precise multi-site mutagenesis on linear DNA fragments
title_short Fast and precise multi-site mutagenesis on linear DNA fragments
title_sort fast and precise multi site mutagenesis on linear dna fragments
topic Multisite mutagenesis
alkaline denaturation
single-stranded DNA
GFP
url https://www.tandfonline.com/doi/10.1080/13102818.2024.2385423
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