@article {Wilbanks169482, author = {Brandon Wilbanks and Cong T. Trinh}, title = {Comprehensive Characterization of Toxicity of Fermentative Metabolites on Microbial Growth}, elocation-id = {169482}, year = {2017}, doi = {10.1101/169482}, publisher = {Cold Spring Harbor Laboratory}, abstract = {Background Volatile carboxylic acids, alcohols, and esters are natural fermentative products, typically derived from anaerobic digestion. These metabolites have important functional roles to regulate cellular metabolisms and broad use as food supplements, flavors and fragrances, solvents, and fuels. Comprehensive characterization of toxic effects of these metabolites on microbial growth under similar conditions is very limited.Results We characterized a comprehensive list of 32 short-chain carboxylic acids, alcohols, and esters on microbial growth of Escherichia coli MG1655 under anaerobic conditions. We analyzed toxic effects of these metabolites on E. coli health, quantified by growth rate and cell mass, as a function of metabolite types, concentrations, and physiochemical properties including carbon chain lengths and associated functional groups, chain branching features, hydrophobicity, and energy density. Strain characterization reveals these metabolites exerted distinct toxic effects on E. coli health. We find that higher concentrations and/or longer carbon lengths of metabolites cause more severe growth inhibition. For the same carbon lengths and metabolite concentrations, alcohols are most toxic followed by acids then esters. We also discover that branched chain metabolites are less toxic than linear chain metabolites for the same carbon lengths and metabolite concentrations. Remarkably, shorter alkyl esters (e.g., ethyl butyrate) are found to be less toxic than longer alkyl esters (e.g., butyl acetate) for the same carbon lengths and metabolite concentrations. Regardless of metabolite types, longer chain metabolites are less soluble and have higher energy densities but are more toxic to microbial growth.Conclusions Metabolite hydrophobicity, correlated with carbon chain length, associated functional group, chain branching feature, and energy density, is a good quantitative index to evaluate toxic effect of a metabolite on microbial health. The results provide better understanding of degrees of toxicity of fermentative metabolites on microbial growth and further help selection of desirable metabolites and hosts for industrial fermentation to overproduce them.μspecific growth rateCXcell concentrationDCWdry cell weightODoptical densityONMEDoctane normalized mass energy densityPipartition coefficient of metabolite iSioctanol and Siwatersolubilities of metabolite i in octanol and water respectivelyttimehhour}, URL = {https://www.biorxiv.org/content/early/2017/07/28/169482}, eprint = {https://www.biorxiv.org/content/early/2017/07/28/169482.full.pdf}, journal = {bioRxiv} }