Chemical-genetic identification of the biochemical targets of polyalkyl guanidinium biocidesElectronic supplementary information (ESI) available: Excel spreadsheet of all chemical-genetic interactions of compounds in yeast and gene-ontology analysis. See DOI: 10.1039/c3ob40593a

Alkylated guanidinium compounds exhibit microbiocidal activity in marine environments, yet the mode of action of these compounds has not been defined. A comprehensive chemical-genetic approach in budding yeast was used to define the biological processes affected by these compounds. N -Butyl- N -decylguanidinium and N -hexyl- N -(3-hydroxypropyl)- N -octylguanidinium chlorides were shown to prevent yeast growth in a dose-dependent manner. All non-essential genes required for tolerance of sub-lethal amounts of these biocides were identified. These unbiased and systematic screens reveal the two related guanidinium compounds have a non-overlapping spectrum of targets in vivo . A functional tryptophan biosynthetic pathway is essential for tolerance of both biocides, which identifies tryptophan amino acid import as one process affected by these compounds. Further analysis of hypersensitive gene lists demonstrates that the substitutions on alkylated guanidiums confer important functional differences in vivo : one derivative renders the ability to generate acidic vacuoles essential, while the other is synthetically lethal with mutants in the transcriptional response to chemical stress. Altogether the results define the common and distinct biological processes affected by biocidal alkylated guanidinium salts. Chemical genetic profiling in yeast defines the biochemical processes targeted by guanidinium-based biocides.