biostudies-literatureTan LLAgency for Science, Technology and ResearchAgency for Science, Technology and Research (A*STAR), SingaporeNational Research FoundationSingapore National Research Foundation (NRF)’s 19th Competitive Research Program486https://www.ebi.ac.uk/biostudies/studies/S-EPMC11048056biostudies-literatureUnknown14(4)In recent years, CRISPR-Cas toolboxes for <i>Streptomyces</i> editing have rapidly accelerated natural product discovery and engineering. However, Cas efficiencies are oftentimes strain-dependent, and the commonly used <i>Streptococcus pyogenes</i> Cas9 (SpCas9) is notorious for having high levels of off-target toxicity effects. Thus, a variety of Cas proteins is required for greater flexibility of genetic manipulation within a wider range of <i>Streptomyces</i> strains. This study explored the first use of <i>Acidaminococcus</i> sp. Cas12j, a hypercompact Cas12 subfamily, for genome editing in <i>Streptomyces</i> and its potential in activating silent biosynthetic gene clusters (BGCs) to enhance natural product synthesis. While the editing efficiencies of Cas12j were not as high as previoBiomoleculesApplication of Cas12j for <i>Streptomyces</i> Editing.PMC11048056C211917003NRF-CRP19-2017-05C233017003Yang LKKanagasundaram YLeong CYKoduru LSeow DCSHeng ELim YHWong FTNg VNg SBPeh GTan LLfalseApplication of Cas12j for <i>Streptomyces</i> Editing.In recent years, CRISPR-Cas toolboxes for <i>Streptomyces</i> editing have rapidly accelerated natural product discovery and engineering. However, Cas efficiencies are oftentimes strain-dependent, and the commonly used <i>Streptococcus pyogenes</i> Cas9 (SpCas9) is notorious for having high levels of off-target toxicity effects. Thus, a variety of Cas proteins is required for greater flexibility of genetic manipulation within a wider range of <i>Streptomyces</i> strains. This study explored the first use of <i>Acidaminococcus</i> sp. Cas12j, a hypercompact Cas12 subfamily, for genome editing in <i>Streptomyces</i> and its potential in activating silent biosynthetic gene clusters (BGCs) to enhance natural product synthesis. While the editing efficiencies of Cas12j were not as high as previo2024-01-01T00:00:00Z2024 Apr2026-04-08T19:48:03.508Z2026-04-08T14:30:54.872ZS-EPMC110480563867250210.3390/biom14040486