(E)-ent-2α-17-Dihydroxy-7,13-Labdadienepentenoic acid

The persistence of pathogenic Escherichia coli under acidic conditions poses a serious risk to food safety, especially in acidic foods such as kimchi. To identify the bacterial factors required for acid resistance, transcriptomic analysis was conducted on an acid-resistant enterotoxigenic E. coli strain and the genes with significant changes in their expression under acidic pH were selected as putative resistance factors against acid stress. These genes included those associated with a glutamatedependent acid resistance (GDAR) system and copper resistance. E. coli strains lacking GadA, GadB, or YbaST, the components of the GDAR system, exhibited significantly attenuated growth and survival under acidic stress conditions. Accordantly, the inhibition of the GDAR system by 3-mercaptopropionic acid and aminooxyacetic acid abolished bacterial adaptation and survival under acidic conditions, indicating the indispensable role of a GDAR system in acid resistance. Intriguingly, the lack of cueR encoding a transcriptional regulator for copper resistance genes markedly impaired bacterial resistance to acid stress as well as copper. Conversely, the absence of YbaST severely compromised bacterial resistance against copper, suggesting an interplay between acid and copper resistance. These results suggest that a GDAR system can be a promising target for developing control measures to prevent E. coli resistance to acid and copper treatments.

This tutorial review showcases recent (2015-2021) work describing ligand construction as it relates to the design of secondary coordination spheres (SCSs). Metalloenzymes, for example, utilize SCSs to stabilize reactive substrates, shuttle small molecules, and alter redox properties, promoting functional activity. In the realm of biomimetic chemistry, specific incorporation of SCS residues (e.g., Brønsted or Lewis acid/bases, crown ethers, redox groups etc.) has been shown to be equally critical to function. This contribution illustrates how fundamental advances in organic and inorganic chemistry have been used for the construction of such SCSs. These imaginative contributions have driven exciting findings in many transformations relevant to clean fuel generation, including small molecule (e.g., H+, N2, CO2, NOx, O2) reduction. In most cases, these reactions occur cooperatively, where both metal and ligand are requisite for substrate activation.

Escherichia coli is an important producer of mono- and di-acids, such as D-lactic acid, itaconic acid, and succinic acid. However, E. coli has limited acid tolerance and requires neutralizers in large-scale fermentation, which leads to increased production costs. Mutagenesis breeding has been shown to be inefficient in improving the acid tolerance of strains. Therefore, it is crucial to analyze the acid resistance mechanism of E. coli. To this end, important regulatory genes and metabolic pathways in the highly evolved acid-resistant E. coli were identified based on transcriptome sequencing. By analyzing the overlap of the genes with significantly different expression levels in the four groups, a synergistic membrane-centric defense mechanism for E. coli against organic acid stress was identified. The mechanism includes four modules: signal perception, energy countermeasures, input conditioning, and envelope reinforcement. In addition, genes related to the ABC transporter pathway, polyketide metabolism, pyrimidine metabolism, and dual-arginine translocation system pathways were found for the first time to be potentially resistant to organic acid stress after overexpression. A new antacid ingredient, RffG, increases the survival rate of E. coli by 4509.6 times. This study provides new clues for improving the performance of acid-tolerant cells and reducing the production cost of industrial organic acid fermentation. KEY POINTS: · Systematic analysis of the mechanism of membrane protein partitioning in E. coli to resist organic acids · TAT system transports correctly folded hydrogenase accessory proteins to resist D-lactic acid stress · Enhanced PG synthesis and weakened hydrolysis to reduce acid penetration into cells · Overexpression of RffG in the polyketide synthesis pathway enhances acid tolerance.