Herramientas y estrategias para diseñar rutas enzimáticas libres de células

The text deals with the technology of enzymes and biocatalysis as green alternatives to the conventional chemical synthesis of chemicals, especially drugs. Enzymes are catalysts that have high specificity and can operate in moderate and environmentally friendly conditions. However, their industrial use has been limited by the problems of using living cells as hosts for the enzymes. For this reason, cell-free synthesis has been developed, which consists of assembling several enzymes from different metabolic pathways to produce molecules of interest without cellular interference. This method offers more flexibility and control to optimize the production system.El texto trata sobre la tecnología de enzimas y la biocatálisis como alternativas verdes a la síntesis química convencional de productos químicos, especialmente fármacos. Las enzimas son catalizadores que tienen una alta especificidad y pueden operar en condiciones moderadas y respetuosas con el medio ambiente. Sin embargo, su uso industrial se ha limitado por los problemas de usar células vivas como huéspedes de las enzimas. Por eso, se ha desarrollado la síntesis sin células, que consiste en ensamblar varias enzimas de diferentes rutas metabólicas para producir moléculas de interés sin interferencias celulares. Este método ofrece más flexibilidad y control para optimizar el sistema de producción

Cellular stress modulates severity of the inflammatory response in lungs via cell surface BiP.

Inflammation is a central pathogenic feature of the acute respiratory distress syndrome (ARDS) in COVID-19. Previous pathologies such as diabetes, autoimmune or cardiovascular diseases become risk factors for the severe hyperinflammatory syndrome. A common feature among these risk factors is the subclinical presence of cellular stress, a finding that has gained attention after the discovery that BiP (GRP78), a master regulator of stress, participates in the SARS-CoV-2 recognition. Here, we show that BiP serum levels are higher in COVID-19 patients who present certain risk factors. Moreover, early during the infection, BiP levels predict severe pneumonia, supporting the use of BiP as a prognosis biomarker. Using a mouse model of pulmonary inflammation, we observed increased levels of cell surface BiP (cs-BiP) in leukocytes during inflammation. This corresponds with a higher number of neutrophiles, which show naturally high levels of cs-BiP, whereas alveolar macrophages show a higher than usual exposure of BiP in their cell surface. The modulation of cellular stress with the use of a clinically approved drug, 4-PBA, resulted in the amelioration of the lung hyperinflammatory response, supporting the anti-stress therapy as a valid therapeutic strategy for patients developing ARDS. Finally, we identified stress-modulated proteins that shed light into the mechanism underlying the cellular stress-inflammation network in lungs