Project description:The purpose of this study was to use chemical similarity evaluations, transcriptional profiling, in vitro toxicokinetic data and physiologically based pharmacokinetic (PBPK) models to support read across for a series of branched carboxylic acids using valproic acid (VPA), a known developmental toxicant, as a comparator. The chemicals included 2-propylpentanoic acid (VPA), 2-ethylbutanoic acid (EBA), 2-ethylhexanoic acid (EHA), 2-methylnonanoic acid (MNA), 2-hexyldecanoic acid (HDA), 2-propylnonanoic acid (PNA), dipentyl acetic acid (DPA) or 2-pentylheptanoic acid (PHA), octanoic acid (OA, a straight chain alkyl acid) and 2-ethylhexanol. Transcriptomics was evaluated in four cell types (A549, HepG2, MCF7 and iCell cardiomyocytes) 6 hours after exposure to 3 concentrations of the compounds, using the L1000 platform. The transcriptional profiling data indicate that two- or three-carbon alkyl substituents at the alpha position of the carboxylic acid (EHA and PNA) elicit a transcriptional profile similar to the one elicited by VPA. The transcriptional profile is different for the other chemicals tested, which provides support for limiting read across from VPA to much shorter and longer acids. Molecular docking models for histone deacetylases, the putative target of VPA, provides a possible mechanistic explanation for the activity cliff elucidated by transcriptomics. In vitro toxicokinetic data was utilized in a PBPK model to estimate internal dosimetry. The PBPK modeling data show that as the branched chain increases, predicted plasma Cmax decreases. This work demonstrates how transcriptomics and other mode of action-based methods can improve read across.
Project description:To elucidate the mechanisms by which the four carboxylic acids—3-phenyllactic acid, lactic acid, L-pyroglutamic acid, and malic acid—inhibit melanin production in B16-F10 cells, a comparative proteomic analysis was conducted to assess changes in protein expression.
Project description:Metatranscriptomic analysis of bioreactor for the anaerobic fermentation of food waste extract and medium chain fatty acids production
Project description:Food waste is a major source of environmental pollution, as its landfills attribute to greenhouse gas emissions. This study developed a robust upcycling bioprocess that converts food waste into lactic acid through autochthonous fermentation and further produces biodegradable polymer polyhydroxybutyrate (PHB). Food can be stored without affecting its bioconversion to lactic acid, making it feasible for industrial application. Mapping autochthonous microbiota in the food waste fermentation before and after storage revealed lactic-acid-producing microorganisms dominate during the indigenous fermentation. Furthermore, through global transcriptomic and gene set enrichment analyses, it was discovered that coupling lactic acid as carbon source with ammonium sulfate as nitrogen source in Cupriavidus necator culture upregulates pathways, including PHB biosynthesis, CO2 fixation, carbon metabolism, pyruvate metabolism, and energy metabolism compared to pairing with ammonium nitrate. There was ∼90 % PHB content in the biomass. Overall, the study provides crucial insights into establishing a bioprocess for food waste repurposing.
Project description:A photocatalytic reaction from tetrazole to nitrile imine, which can be coupled with carboxylic acids in aqueous solvents, has been developed. The reaction has been successfully used for photocatalyst-dependent labeling of carboxylic acids in proteins.