Zymomonas mobilis ZM4 utilizes an acetaldehyde dehydrogenase to produce acetate

Zymomonas mobilis is a promising bacterial host for biofuel production but further improvement has been hindered because some aspects of its metabolism remain poorly understood. For example, one of the main byproducts generated by Z. mobilis is acetate but the pathway for acetate production is unknown. Acetaldehyde oxidation has been proposed as the major source of acetate and an acetaldehyde dehydrogenase was previously isolated from Z. mobilis via activity guided fractionation, but the corresponding gene has never been identified. We determined that the locus ZMO1754 (also known as ZMO_RS07890) encodes an NADP+-dependent acetaldehyde dehydrogenase that is responsible for acetate production by Z. mobilis. Deletion of this gene from the chromosome resulted in a growth defect in oxic conditions, suggesting that acetaldehyde detoxification is an important role of acetaldehyde dehydrogenase. The deletion strain also exhibited a near complete abolition of acetate production, both in typical laboratory conditions and during lignocellulosic hydrolysate fermentation. Our results show that ZMO1754 encodes the major acetaldehyde dehydrogenase in Z. mobilis and we therefore rename the gene aldB based on functional similarity to the Escherichia coli acetaldehyde dehydrogenase.

NADPH is important for isobutanol tolerance in a minimal medium of Saccharomyces cerevisiae

We showed that the isobutanol sensitivity in glucose-6-phosphate dehydrogenase-deficient cells of the yeast Saccharomyces cerevisiae was rescued by an alternative NADPH producer, acetaldehyde dehydrogenase, but not in the cells lacking 6-phosphogluconate dehydrogenase. This phenotype correlated with the intracellular NADPH/NADP+ ratio in yeast strains. Our findings indicate the importance of NADPH for the isobutanol tolerance of yeast cells.

Mir-23b down-regulates the expression of target gene of acetaldehyde dehydrogenase 1a1 and increases the sensitivity of cervical cancer stem cells to cisplatin

Purpose: To study the effect of miR-23b on the expression of the target gene of acetaldehyde dehydrogenase 1A1 (ALDH1A1), and cisplatin (CDDP) susceptibility of cervical carcinoma stem cells. Methods: Human cervical cancer cell line Hela cells were cultured in vitro, and miR-23b mimic and negative control were transfected into the cells using lipofectamine method. The growth of the two groups of cells was determined using growth curve method, and their proliferation measured using plate clone formation. The influence of treatments on the sensitivity of the cells to CDDP was assayed using MTT method. The mRNA expression of ALDH1A1 in Hela cells was assayed using real-time quantitative polymerase hain reation (PCR), while its protein expression was assayed by Western blot. Results: The levels of expressions of ALDH1A1 protein and mRNA in the miR-23b overexpression group were significantly lower than those in the control group (p < 0.05). The sensitivities of Hela cells to CDDP in the ALDH1A1 inhibition group and the control group were dose-dependent to some extent, but cell inhibition in ALDH1A1 inhibition group markedly increased, relative to control when the CDDP dose was 0.1 ppc (p < 0.01). Conclusion: Up-regulating the expression of miR-23b significantly inhibits the growth and proliferation of cervical cancer cells, and increases their sensitivity to CDDP via down-regulation of the expression of the target gene for ALDH1A1. Therefore, during cervical carcinoma treatment, increasing the level of miR-23b may produce a chemotherapeutic effect. Keywords: MiR-23b, Acetaldehyde dehydrogenase 1A1, Cervical cancer, Cisplatin, Sensitivity

Investigating the reaction and substrate preference of indole-3-acetaldehyde dehydrogenase from the plant pathogen Pseudomonas syringae PtoDC3000

Aldehyde dehydrogenases (ALDHs) catalyze the conversion of various aliphatic and aromatic aldehydes into corresponding carboxylic acids. Traditionally considered as housekeeping enzymes, new biochemical roles are being identified for members of ALDH family. Recent work showed that AldA from the plant pathogen Pseudomonas syringae strain PtoDC3000 (PtoDC3000) functions as an indole-3-acetaldehyde dehydrogenase for the synthesis of indole-3-acetic acid (IAA). IAA produced by AldA allows the pathogen to suppress salicylic acid-mediated defenses in the model plant Arabidopsis thaliana. Here we present a biochemical and structural analysis of the AldA indole-3-acetaldehyde dehydrogenase from PtoDC3000. Site-directed mutants targeting the catalytic residues Cys302 and Glu267 resulted in a loss of enzymatic activity. The X-ray crystal structure of the catalytically inactive AldA C302A mutant in complex with IAA and NAD+ showed the cofactor adopting a conformation that differs from the previously reported structure of AldA. These structures suggest that NAD+ undergoes a conformational change during the AldA reaction mechanism similar to that reported for human ALDH. Site-directed mutagenesis of the IAA binding site indicates that changes in the active site surface reduces AldA activity; however, substitution of Phe169 with a tryptophan altered the substrate selectivity of the mutant to prefer octanal. The present study highlights the inherent biochemical versatility of members of the ALDH enzyme superfamily in P. syringae.

Hydnora africana Derived Phytochemicals against Acetaldehyde Dehydrogenase of Aeromonas hydrophila Causing Septicemia

For drug discovery it takes approximately 6 years to expose in the market and for commercial uses. There are different procedure to get success in the drug discovery like preliminary phytochemical analysis, structural elucidation of the bioactive compound, preclinical test and clinical test etc. So to optimize the time for invention of new drug molecule, computer aided drug designing and molecular docking analysis is being used as one of the highly effective methodology. The phytochemical extraction of Hydnora africana plant was reported to inhibit the growth of Aeromonas hydrophila which cause Septicemia. “Biovia Discovery Studio” molecular docking methods give us opportunity to identify the effective molecule against the microbes. “High positive values of -CDOCKER energy and -CDOCKER interaction energy” recommended that flavone can effectively deactivate the acetaldehyde dehydrogenase enzyme thereby interrupting the life cycle of the organism.

Acetaldehyde dehydrogenase 2 deficiency increases mitochondrial reactive oxygen species emission and induces mitochondrial protease Omi/HtrA2 in skeletal muscle

Acetaldehyde dehydrogenase 2 (ALDH2) is an enzyme involved in redox homeostasis as well as the detoxification process in alcohol metabolism. Nearly 8% of the world’s population have an inactivating mutation in the ALDH2 gene. However, the expression patterns and specific functions of ALDH2 in skeletal muscles are still unclear. Herein, we report that ALDH2 is expressed in skeletal muscle and is localized to the mitochondrial fraction. Oxidative muscles had a higher amount of ALDH2 protein than glycolytic muscles. We next comprehensively investigated whether ALDH2 knockout in mice induces mitochondrial adaptations in gastrocnemius muscle (for example, content, enzymatic activity, respiratory function, supercomplex formation, and functional networking). We found that ALDH2 deficiency resulted in partial mitochondrial dysfunction in gastrocnemius muscle because it increased mitochondrial reactive oxygen species (ROS) emission (2′,7′-dichlorofluorescein and MitoSOX oxidation rate during respiration) and the frequency of regional mitochondrial depolarization. Moreover, we determined whether ALDH2 deficiency and the related mitochondrial dysfunction trigger mitochondrial stress and quality control responses in gastrocnemius muscle (for example, mitophagy markers, dynamics, and the unfolded protein response). We found that ALDH2 deficiency upregulated the mitochondrial serine protease Omi/HtrA2 (a marker of the activation of a branch of the mitochondrial unfolded protein response). In summary, ALDH2 deficiency leads to greater mitochondrial ROS production, but homeostasis can be maintained via an appropriate stress response.