Epoxide hydrolases (EHs; 3.3.2.x) catalyze the enantioselective ring opening of racemic epoxides to the corresponding enantiopure vicinal diols and remaining equivalent unreacted epoxides. These epoxides and diols are used for the synthesis of chiral drug intermediates. With an upsurge in the methods for identification of novel microbial EHs, a lot of EHs have been discovered and utilized for kinetic resolution of racemic epoxides. However, there is still a constraint on the account of limited EHs being successfully applied on the preparative scale for industrial biotransformations. This limitation has to be overcome before application of identified functional EHs on large scale. Many strategies such as optimizing reaction media, immobilizing EHs and laboratory-scale directed evolution of EHs have been adopted for enhancing the industrial potential of EHs. In this review, these approaches have been highlighted which can serve as a pathway for the enrichment of already identified EHs for their application on an industrial scale in future studies.
In order to produce enantiomerically pure epoxides for the synthesis of value-added chemicals, a novel putative epoxide hydrolase (EH) sgeh was cloned and overexpressed in pET28a/Escherichia coli BL21(DE3). The 1047 bp sgeh gene was mined from Streptomyces griseus NBRC 13350 genome sequence. The recombinant hexahistidyl-tagged SGEH was purified (16.6-fold) by immobilized metal-affinity chromatography, with 90% yield as a homodimer of 100 kDa. The recombinant E. coli whole cells overexpressing SGEH could kinetically resolve racemic phenyl glycidyl ether (PGE) into (R)-PGE with 98% ee, 40% yield, and enantiomeric ratio (E) of 20. This was achieved under the optimized reaction conditions i.e. cell/substrate ratio of 20:1 (w/w) at pH 7.5 and 20 °C in 10% (v/v) dimethylformamide (DMF) in a 10 h reaction. 99% enantiopure (R)-PGE was obtained when the reaction time was prolonged to 12 h with a yield of 34%. In conclusion, an economically viable and environment friendly green process for the production of enantiopure (R)-PGE was developed by using wet cells of E. coli expressing recombinant SGEH.
By the end of the year 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) originated in China. With the passage of more than half of the year 2020, the virus has spread worldwide, making it the worst pandemic of our lifetime. The spread of the virus is controlled by imposing lockdown, which has led to severe economic slowdown around the globe. Coronaviruses are zoonotic as they spread from animals to humans. Factors such as rapid urbanization and poultry farming have permitted inter-mixing of species leading to crossing barriers and spreading of viruses to humans. Coronavirus disease (COVID-19) caused by SARS-CoV-2 is acute in most people, but it may progress to severe respiratory distress, especially in people with weak innate immunity leading to death. It is a contagious infection with the death toll mounting to above seven lakhs in the world, so there is an urgent need to find the vaccine to cure the virus, as there is no licensed drug or vaccine available. Global collaborations and increased research efforts among the scientific community have led to more than 150 clinical trials globally. This review discusses the SARS-CoV-2 replication mechanism and potential vaccine candidates in phase III COVID-19 clinical trials. Measures adopted to accomplish the fast pace of the COVID-19 trials are highlighted with an update on possible new drug targets or strategies to fight off the virus.
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