RESUMEN
Quality of processes and products is based on traceability and review of both components, material processing and product flow throughout the manufacturing and supply chain. Blockchain technology enables cross-border audit trail and traceability while reducing costs. Donors are the providers of biological raw material (starting material). They can share their health records when donating by using an IPS document or a FHIR Questionnaire-response resource. It allows health personnel to retrieve and verify relevant clinical information when donating. Additionally, health personnel can generate an anonymized and de-identified digital twin of the donor for research purposes, and it can be updated over time. The starting material can include a reference to a digital twin of an unknown supplier, which improves the data quality and enhances research possibilities. Adverse reactions and events can be also recorded on blockchain to improve safety, transparency, traceability, medical research and product quality.
Asunto(s)
Investigación Biomédica , Cadena de Bloques , Humanos , Comercio , Exactitud de los Datos , Personal de SaludRESUMEN
Phytosterols, generated as a by-product of vegetable oils or wood pulp, contain the cyclopentane-perhydro-phenanthrene nucleus, and can be converted into steroid intermediates by removing the C17 side chain. This chapter shows the scale-up, from flask to fermentor, of the phytosterols bioconversion into 4-androstene-3,17-dione (androstenedione; AD) with Mycobacterium neoaurum B-3805. Due to the fact that phytosterols and AD are nearly insoluble in water, two-phase systems and the use of chemically modified cyclodextrins have been described as methods to solve it. Here we use a water-oil two-phase system that allows for the bioconversion of up to 20 g/L of phytosterols into AD in 20 L fermentor.
Asunto(s)
Androstenodiona/biosíntesis , Biotransformación , Mycobacterium/genética , Fitosteroles/química , Androstenodiona/química , Mycobacterium/metabolismo , Aceites de Plantas/química , Glycine max/química , Agua/químicaRESUMEN
A number of pharmaceutical steroid synthons are currently produced through the microbial side-chain cleavage of natural sterols as an alternative to multi-step chemical synthesis. Industrially, these synthons have been usually produced through fermentative processes using environmental isolated microorganisms or their conventional mutants. Mycobacterium smegmatis mc2 155 is a model organism for tuberculosis studies which uses cholesterol as the sole carbon and energy source for growth, as other mycobacterial strains. Nevertheless, this property has not been exploited for the industrial production of steroidic synthons. Taking advantage of our knowledge on the cholesterol degradation pathway of M. smegmatis mc2 155 we have demonstrated that the MSMEG_6039 (kshB1) and MSMEG_5941 (kstD1) genes encoding a reductase component of the 3-ketosteroid 9α-hydroxylase (KshAB) and a ketosteroid Δ1 -dehydrogenase (KstD), respectively, are indispensable enzymes for the central metabolism of cholesterol. Therefore, we have constructed a MSMEG_6039 (kshB1) gene deletion mutant of M. smegmatis MS6039 that transforms efficiently natural sterols (e.g. cholesterol and phytosterols) into 1,4-androstadiene-3,17-dione. In addition, we have demonstrated that a double deletion mutant M. smegmatis MS6039-5941 [ΔMSMEG_6039 (ΔkshB1) and ΔMSMEG_5941 (ΔkstD1)] transforms natural sterols into 4-androstene-3,17-dione with high yields. These findings suggest that the catabolism of cholesterol in M. smegmatis mc2 155 is easy to handle and equally efficient for sterol transformation than other industrial strains, paving the way for valuating this strain as a suitable industrial cell factory to develop à la carte metabolic engineering strategies for the industrial production of pharmaceutical steroids.