Optimizing the CRISPR/Cas9 system for gene editing in Yarrowia lipolytica

Yarrowia lipolytica is a promising host for producing valuable chemicals owing to its robustness and metabolic versatility. Efficient genome editing tools are essential for advancing its biotechnological applications. Although CRISPR/Cas9 technology has been applied in Y. lipolytica, achieving a con...

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Main Authors: Jianhui Liu, Yamin Zhu, Jin Hou
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:Engineering Microbiology
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Online Access:http://www.sciencedirect.com/science/article/pii/S2667370325000050
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author Jianhui Liu
Yamin Zhu
Jin Hou
author_facet Jianhui Liu
Yamin Zhu
Jin Hou
author_sort Jianhui Liu
collection DOAJ
description Yarrowia lipolytica is a promising host for producing valuable chemicals owing to its robustness and metabolic versatility. Efficient genome editing tools are essential for advancing its biotechnological applications. Although CRISPR/Cas9 technology has been applied in Y. lipolytica, achieving a consistently high editing performance remains challenging owing to the low homologous recombination efficiency and variability in system components. In this study, we optimized CRISPR/Cas9-mediated genome editing in Y. lipolytica to enhance its editing efficiency. Using the RNA polymerase III promoter SCR1-tRNA for sgRNA expression, we achieved a gene disruption efficiency of 92.5 %. The tRNA-sgRNA architecture enabled a dual gene disruption efficiency of 57.5 %. KU70 deletion in the Cas9 system increased the integration efficiency to 92.5 %, and Rad52 and Sae2 overexpression boosted homologous recombination. The introduction of Cas9D147Y, P411T (iCas9) enhanced the efficiency of both gene disruption and genome integration. This study provides a powerful tool for efficient gene editing in Y. lipolytica, which will accelerate the construction of yeast cell factories.
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institution Kabale University
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publishDate 2025-06-01
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series Engineering Microbiology
spelling doaj-art-a5d499c593204e6ca86de67d5c9eeb872025-08-20T03:30:30ZengElsevierEngineering Microbiology2667-37032025-06-015210019310.1016/j.engmic.2025.100193Optimizing the CRISPR/Cas9 system for gene editing in Yarrowia lipolyticaJianhui Liu0Yamin Zhu1Jin Hou2State Key Laboratory of Microbial Technology, Shandong University, Qingdao 266237, ChinaState Key Laboratory of Microbial Technology, Shandong University, Qingdao 266237, ChinaCorresponding author.; State Key Laboratory of Microbial Technology, Shandong University, Qingdao 266237, ChinaYarrowia lipolytica is a promising host for producing valuable chemicals owing to its robustness and metabolic versatility. Efficient genome editing tools are essential for advancing its biotechnological applications. Although CRISPR/Cas9 technology has been applied in Y. lipolytica, achieving a consistently high editing performance remains challenging owing to the low homologous recombination efficiency and variability in system components. In this study, we optimized CRISPR/Cas9-mediated genome editing in Y. lipolytica to enhance its editing efficiency. Using the RNA polymerase III promoter SCR1-tRNA for sgRNA expression, we achieved a gene disruption efficiency of 92.5 %. The tRNA-sgRNA architecture enabled a dual gene disruption efficiency of 57.5 %. KU70 deletion in the Cas9 system increased the integration efficiency to 92.5 %, and Rad52 and Sae2 overexpression boosted homologous recombination. The introduction of Cas9D147Y, P411T (iCas9) enhanced the efficiency of both gene disruption and genome integration. This study provides a powerful tool for efficient gene editing in Y. lipolytica, which will accelerate the construction of yeast cell factories.http://www.sciencedirect.com/science/article/pii/S2667370325000050CRISPR/Cas9 technologyYarrowia lipolyticasgRNA promoterCas9 expression strategyMultiplex gene editingGenome integration
spellingShingle Jianhui Liu
Yamin Zhu
Jin Hou
Optimizing the CRISPR/Cas9 system for gene editing in Yarrowia lipolytica
Engineering Microbiology
CRISPR/Cas9 technology
Yarrowia lipolytica
sgRNA promoter
Cas9 expression strategy
Multiplex gene editing
Genome integration
title Optimizing the CRISPR/Cas9 system for gene editing in Yarrowia lipolytica
title_full Optimizing the CRISPR/Cas9 system for gene editing in Yarrowia lipolytica
title_fullStr Optimizing the CRISPR/Cas9 system for gene editing in Yarrowia lipolytica
title_full_unstemmed Optimizing the CRISPR/Cas9 system for gene editing in Yarrowia lipolytica
title_short Optimizing the CRISPR/Cas9 system for gene editing in Yarrowia lipolytica
title_sort optimizing the crispr cas9 system for gene editing in yarrowia lipolytica
topic CRISPR/Cas9 technology
Yarrowia lipolytica
sgRNA promoter
Cas9 expression strategy
Multiplex gene editing
Genome integration
url http://www.sciencedirect.com/science/article/pii/S2667370325000050
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AT yaminzhu optimizingthecrisprcas9systemforgeneeditinginyarrowialipolytica
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