Biotransformación bacteriana de esteroides

Abstract

Steroid compounds are a family of molecules of great biological importance due to their abundance in nature and their participation in a wide range of cellular and physiological functions in different organisms (Lednicer, 2011; Nelson and Cox, 2012). Since the mid-twentieth century, the number of steroid molecules has increased considerably due to the chemical synthesis of a large number of xenobiotic compounds with different pharmacological properties. The study of microbial pathways of steroid degradation has aroused great interest in the scientific community in recent decades, driven by the abundance of natural steroids and the considerable increase of xenobiotic steroid contaminants in the environment (García et al., 2012). A considerable number of these studies have been performed with Actinobacteria (Actinomycetes) and in particular, with representatives of the suborder Corynebacterineae such as Mycobacterium, Rhodococcus and Gordonia. These genera include pathogenic bacteria such as Mycobacterium tuberculosis or Rhodococcus equi, and non-strictly pathogenic or saprophyte bacteria such as Mycobacterium smegmatis, Gordonia neofelifaecis and Rhodococcus jostii. The most important advances in this field have been achieved in the study of cholesterol catabolism, largely due to the role of this molecule in the pathogenesis of M. tuberculosis. However, actinobacteria usually contain several gene clusters involved in the steroid catabolism, which confer on them the ability to mineralize a wide range of steroids (e. g., sterols, bile acids, testosterone, progesterone). The complexity of the steroid molecules and consequently of their degradation processes makes the study of these pathways especially difficult. On the other hand, microbial biocatalysts have been used for decades to facilitate the synthesis of new steroid molecules in the pharmaceutical industry (Donova and Egorova, 2012). For this purpose, different environmentally isolated microorganisms improved by means of conventional random mutation and selection techniques have been traditionally used in biotransformation processes. However, it has recently begun to explore the implementation of Metabolic Engineering and Synthetic Biology approaches for the development of improved biocatalysts à la carte. In this way, in recent years there has been a convergence of interests between the study of steroid catabolic pathways and the design of biocatalysts á la carte for industrial purposes. This Doctoral Thesis is part of this new experimental approach...