Data availability Transcriptomic data have been deposited in the NCBI Sequence Read Archive under BioProject accession PRJNA1001058 . The proteins used to construct the phylogenetic tree ( https://doi.org/10.6084/m9.figshare.31680328 ) and the mass spectrometry data ( https://doi.org/10.6084/m9.figshare.31680478 ) are publicly available on Figshare 41 , 42 . Uncropped images of gels and blots are presented in Supplementary Fig. 1 . Source data are provided for Figs. 1c,d and 2i,l and Extended Data Figs. 1c , 2a–d , 4a,b, 5a,b and 9c,d . Amino acid alignments of AcrVA2 homologues are publicly available on Figshare ( https://doi.org/10.6084/m9.figshare.31684630 ) 43 . Sequences of AcrVA2 homologues used to generate these amino acid alignments are listed in Supplementary Table 2 . Nucleotide alignments of different cas12a variants downregulated by AcrVA2 are publicly available on Figshare ( https://doi.org/10.6084/m9.figshare.31684813 ) 44 . Source data are provided with this paper.…