Catabolism and biotechnological applications of cholesterol degrading bacteria

Abstract

Cholesterol is a steroid commonly found in nature with a great relevance in biology, medicine and chemistry, playing an essential role as a structural component of animal cell membranes. The ubiquity of cholesterol in the environment has made it a reference biomarker for environmental pollution analysis and a common carbon source for different microorganisms, some of them being important pathogens such as Mycobacterium tuberculosis. This work revises the accumulated biochemical and genetic knowledge on the bacterial pathways that degrade or transform this molecule, given that the characterization of cholesterol metabolism would contribute not only to understand its role in tuberculosis but also to develop new biotechnological processes that use this and other related molecules as starting or target materials.

Figure 1

Chemical structures of cholesterol and some derived natural molecules.

Figure 2

Proposed pathway for cholesterol degradation under aerobic conditions. Cholest‐4‐en‐3‐one or any of the subsequent metabolites from degradation of the side‐chain up to (and including) AD may undergo a dehydrogenation reaction to introduce a double bond in the position 1, leading to compound cholest‐1,4‐diene‐3‐one in the case of cholest‐4‐en‐3‐one, or to the corresponding 1,2‐dehydro derivatives for other molecules. The side‐chain degradation of this compounds will be identical to that of the cholest‐4‐en‐3‐one to the common intermediate 9α‐hydroxyandrosta‐1,4‐diene‐3,17‐dione. The microorganisms from which enzymes implicated in different steps are indicated by numbers. Numbers in brackets are assigned arbitrarily to facilitate the compound identification in the text.

Figure 3

Proposed β‐oxidation‐like reactions for cholesterol side‐chain degradation. The Fad proteins have been assigned according to the nomenclature of the E. coli genes involved in the β‐oxidation of fatty acids. LiuE is the name assigned to 3‐hydroxy‐3‐methylglutaryl‐coenzyme A lyases.

Figure 4

Organization of the main gene clusters implied or suggested to be involved in the degradation of cholesterol in M. smegmatis mc²155. The identity number for each MSMEG gene is indicated within the arrows. The name of some genes of interest is written above them. Numbers below genes indicate the number of bp between adjacent genes; numbers in brackets indicate separation and numbers in parentheses indicate overlap. Numbers above diagonal lines indicate the genomic position in kb. Orange: mce cluster. Green: genes suggested and/or proved to participate in the side‐chain degradation. Blue: genes suggested and/or proved to participate in the central or lower catabolic pathway. Yellow: genes coding the transcriptional repressors KstR and KstR2. Genes surrounded by a dashed line are controlled by KstR2, the rest of the genes showed in this figure are controlled by KstR (except for MSMEG_5905, 5909, 5910, 5912, 5916, 5917, 5924, 5926, 5928, 5936, 5938, 6005, 6006, 6007, 6010, 6034, which could not be proved to be controlled by any of both repressors) (Kendall et al., 2007; 2010; Uhía et al., 2012).