Design of an Effective sgRNA for CRISPR/Cas9 Knock-Ins and Full Mutant Segregation in Polyploid <i>Synechocystis</i> sp. PCC 6803

<i>Synechocystis</i> sp. PCC 6803 is a highly promising organism for the production of diverse recombinant compounds, including biofuels. However, conventional genetic engineering in <i>Synechocystis</i> presents challenges due to its highly polyploid genome, which not only r...

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Main Authors: Maria Isabel Nares-Rodriguez, Esther Karunakaran
Format: Article
Language:English
Published: MDPI AG 2025-01-01
Series:SynBio
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Online Access:https://www.mdpi.com/2674-0583/3/1/3
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author Maria Isabel Nares-Rodriguez
Esther Karunakaran
author_facet Maria Isabel Nares-Rodriguez
Esther Karunakaran
author_sort Maria Isabel Nares-Rodriguez
collection DOAJ
description <i>Synechocystis</i> sp. PCC 6803 is a highly promising organism for the production of diverse recombinant compounds, including biofuels. However, conventional genetic engineering in <i>Synechocystis</i> presents challenges due to its highly polyploid genome, which not only results in low product yields but also compromises the reliability of recombinant strains for biomanufacturing applications. The CRISPR/Cas9 system, renowned for its precision, efficiency, and versatility across a wide range of chassis, offers significant potential to address the limitations posed by polyploid genomes. In this study, we developed and optimized an effective sgRNA for the targeted knock-in of nucleotide sequences of varying lengths into the neutral locus <i>slr</i>0168 of polyploid <i>Synechocystis</i> using CRISPR/Cas9. The gene encoding di-geranylgeranylglycerophospholipid reductase from <i>Sulfolobus acidocaldarius</i> and the methyl ketone operon from <i>Solanum habrochaites</i> were chosen as the exemplar nucleotide sequences for incorporation into the chromosome of <i>Synechocystis.</i> Our results demonstrate that the designed sgRNA effectively facilitated both knock-in events and that CRISPR/Cas9 enabled complete mutant segregation in a single round of selection and induction.
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spelling doaj-art-b5b23a2ed8304b60ac80668d3d108a2d2025-08-20T03:43:51ZengMDPI AGSynBio2674-05832025-01-0131310.3390/synbio3010003Design of an Effective sgRNA for CRISPR/Cas9 Knock-Ins and Full Mutant Segregation in Polyploid <i>Synechocystis</i> sp. PCC 6803Maria Isabel Nares-Rodriguez0Esther Karunakaran1School of Chemical, Materials and Biological Engineering, University of Sheffield, Sheffield S1 3JD, UKSchool of Chemical, Materials and Biological Engineering, University of Sheffield, Sheffield S1 3JD, UK<i>Synechocystis</i> sp. PCC 6803 is a highly promising organism for the production of diverse recombinant compounds, including biofuels. However, conventional genetic engineering in <i>Synechocystis</i> presents challenges due to its highly polyploid genome, which not only results in low product yields but also compromises the reliability of recombinant strains for biomanufacturing applications. The CRISPR/Cas9 system, renowned for its precision, efficiency, and versatility across a wide range of chassis, offers significant potential to address the limitations posed by polyploid genomes. In this study, we developed and optimized an effective sgRNA for the targeted knock-in of nucleotide sequences of varying lengths into the neutral locus <i>slr</i>0168 of polyploid <i>Synechocystis</i> using CRISPR/Cas9. The gene encoding di-geranylgeranylglycerophospholipid reductase from <i>Sulfolobus acidocaldarius</i> and the methyl ketone operon from <i>Solanum habrochaites</i> were chosen as the exemplar nucleotide sequences for incorporation into the chromosome of <i>Synechocystis.</i> Our results demonstrate that the designed sgRNA effectively facilitated both knock-in events and that CRISPR/Cas9 enabled complete mutant segregation in a single round of selection and induction.https://www.mdpi.com/2674-0583/3/1/3CRISPR/Cas9sgRNA designfull mutant segregation<i>Synechocystis</i> sp. PCC 6803single induction step
spellingShingle Maria Isabel Nares-Rodriguez
Esther Karunakaran
Design of an Effective sgRNA for CRISPR/Cas9 Knock-Ins and Full Mutant Segregation in Polyploid <i>Synechocystis</i> sp. PCC 6803
SynBio
CRISPR/Cas9
sgRNA design
full mutant segregation
<i>Synechocystis</i> sp. PCC 6803
single induction step
title Design of an Effective sgRNA for CRISPR/Cas9 Knock-Ins and Full Mutant Segregation in Polyploid <i>Synechocystis</i> sp. PCC 6803
title_full Design of an Effective sgRNA for CRISPR/Cas9 Knock-Ins and Full Mutant Segregation in Polyploid <i>Synechocystis</i> sp. PCC 6803
title_fullStr Design of an Effective sgRNA for CRISPR/Cas9 Knock-Ins and Full Mutant Segregation in Polyploid <i>Synechocystis</i> sp. PCC 6803
title_full_unstemmed Design of an Effective sgRNA for CRISPR/Cas9 Knock-Ins and Full Mutant Segregation in Polyploid <i>Synechocystis</i> sp. PCC 6803
title_short Design of an Effective sgRNA for CRISPR/Cas9 Knock-Ins and Full Mutant Segregation in Polyploid <i>Synechocystis</i> sp. PCC 6803
title_sort design of an effective sgrna for crispr cas9 knock ins and full mutant segregation in polyploid i synechocystis i sp pcc 6803
topic CRISPR/Cas9
sgRNA design
full mutant segregation
<i>Synechocystis</i> sp. PCC 6803
single induction step
url https://www.mdpi.com/2674-0583/3/1/3
work_keys_str_mv AT mariaisabelnaresrodriguez designofaneffectivesgrnaforcrisprcas9knockinsandfullmutantsegregationinpolyploidisynechocystisisppcc6803
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