Advances in degradation mechanisms of 1,2,3-trichloropropane and remediation technology of contaminated sites / 生物工程学报

1,2,3-trichloropropane (TCP) is an industrially synthesized aliphatic chlorinated hydrocarbon and an intermediate product in the industrial production of epichlorohydrin, which can be used as a precursor for the manufacture of soil fumigant and organic solvents. Due to its biological toxicity, environmental persistence and strong environmental migration ability, 1,2,3-TCP is listed as an emerging organochlorine pollutant in the environment and regulated by many international organizations. Currently, the degradation of 1,2,3-TCP and the remediation of 1,2,3-TCP-contaminated sites receive great attention, but the degradation mechanism of 1,2,3-TCP has not been summarized in depth. This article discussed the origin of 1,2,3-TCP, its environmental impact and ecological effects, and the physical and chemical degradation techniques. This was followed by summarizing the degradation mechanisms of 1,2,3-TCP (e.g., aerobic co-biodegradation, anaerobic biodegradation). Specially, the pathways and mechanisms of microbial biodegradation and transformation of 1,2,3-TCP in anoxic environments (e.g., groundwater) were thoroughly reviewed. The feasibility of using 1,2,3-TCP as an electron acceptor by organohalide-respiring bacteria under anoxic conditions was predicted based on thermodynamic analysis. Last but not least, in situ bioremediation of 1,2,3-TCP contaminated sites was summarized, and prospects for future research were discussed.

Discovery of direct inhibitors of Keap1-Nrf2 protein-protein interaction as potential therapeutic and preventive agents

The Keap1-Nrf2-ARE pathway is an important antioxidant defense mechanism that protects cells from oxidative stress and the Keap1-Nrf2 protein-protein interaction (PPI) has become an important drug target to upregulate the expression of ARE-controlled cytoprotective oxidative stress response enzymes in the development of therapeutic and preventive agents for a number of diseases and conditions. However, most known Nrf2 activators/ARE inducers are indirect inhibitors of Keap1-Nrf2 PPI and they are electrophilic species that act by modifying the sulfhydryl groups of Keap1׳s cysteine residues. The electrophilicity of these indirect inhibitors may cause "off-target" side effects by reacting with cysteine residues of other important cellular proteins. Efforts have recently been focused on the development of direct inhibitors of Keap1-Nrf2 PPI. This article reviews these recent research efforts including the development of high throughput screening assays, the discovery of peptide and small molecule direct inhibitors, and the biophysical characterization of the binding of these inhibitors to the target Keap1 Kelch domain protein. These non-covalent direct inhibitors of Keap1-Nrf2 PPI could potentially be developed into effective therapeutic or preventive agents for a variety of diseases and conditions.