Degradation of Bile Acids by Soil and Water Bacteria

Abstract

Bile acids are surface-active steroid compounds with a C5 carboxylic side chain at the steroid nucleus. They are produced by vertebrates, mainly functioning as emulsifiers for lipophilic nutrients, as signaling compounds, and as an antimicrobial barrier in the duodenum. Upon excretion into soil and water, bile acids serve as carbon- and energy-rich growth substrates for diverse heterotrophic bacteria. Metabolic pathways for the degradation of bile acids are predominantly studied in individual strains of the genera Pseudomonas, Comamonas, Sphingobium, Azoarcus, and Rhodococcus. Bile acid degradation is initiated by oxidative reactions of the steroid skeleton at ring A and degradation of the carboxylic side chain before the steroid nucleus is broken down into central metabolic intermediates for biomass and energy production. This review summarizes the current biochemical and genetic knowledge on aerobic and anaerobic degradation of bile acids by soil and water bacteria. In addition, ecological and applied aspects are addressed, including resistance mechanisms against the toxic effects of bile acids.

Investigations on the Degradation of the Bile Salt Cholate via the 9,10-Seco-Pathway Reveals the Formation of a Novel Recalcitrant Steroid Compound by a Side Reaction in Sphingobium sp. Strain Chol11

“…Aerobic bacterial degradation of 7-hydroxy bile salts in soil and water can proceed via two pathway variants, namely the Δ 1,4 -variant and the Δ 4,6 -variant [6]. The Δ 4,6 -variant…”

“…A total of 95% of bile salts are recycled in the enterohepatic cycle, but a certain amount is not reabsorbed and therefore excreted with feces and urine, e.g., 400-600 mg bile salts per day and human [3]. Once released into the environment, bile salts are subject to bacterial degradation [4][5][6] (Figure 1A). As shown for the model organisms Pseudomonas stutzeri Chol1 [7], Comamonas testosteroni TA41 [8], and Rhodococcus jostii RHA1 [9], bile salts can be degraded via the 9,10-seco-pathway for steroid degradation that involves ∆ 1,4 -3-keto intermediates and will therefore be referred to as ∆ 1, 4 -variant (see the work of [4,6,10] and references therein): In the first steps of this well-elucidated pathway, the A-ring of the steroid skeleton is oxidized to a ∆ 1,4 -3-keto-structure (III in Figure 1).…”

“…Once released into the environment, bile salts are subject to bacterial degradation [4][5][6] (Figure 1A). As shown for the model organisms Pseudomonas stutzeri Chol1 [7], Comamonas testosteroni TA41 [8], and Rhodococcus jostii RHA1 [9], bile salts can be degraded via the 9,10-seco-pathway for steroid degradation that involves ∆ 1,4 -3-keto intermediates and will therefore be referred to as ∆ 1, 4 -variant (see the work of [4,6,10] and references therein): In the first steps of this well-elucidated pathway, the A-ring of the steroid skeleton is oxidized to a ∆ 1,4 -3-keto-structure (III in Figure 1). Simultaneously, the side chain is degraded via β-oxidation and aldolytic reactions leading to side chain-less androsta-1,4-diene-3,17-diones (ADDs; e.g., 12β-DHADD, IV in Figure 1, in the degradation of cholate).…”

“…The A-ring is cleaved by consecutive hydroxylation and meta-cleavage similar to degradation of aromatic compounds [15][16][17][18]. The intermediate with opened A-and B-rings is then further degraded via hydrolytic and β-oxidation reactions (see [6,10] and references therein). Genes for degrading bile salts via this pathway are widespread in many bacterial species and metagenomes from different environments [19,20].…”

“…strain Chol11, formerly Novosphingobium sp. strain Chol11, that proceeds via intermediates with a 3-keto-∆ 4,6structure of the steroid skeleton and is therefore referred to as ∆ 4,6 -variant [21][22][23]. After A-ring oxidation leading to ∆ 4 -3-keto-cholate (II) during the degradation of cholate [24], a further double bond is inserted into the B-ring upon elimination of the 7OH by the dehydratase Hsh2 [22], leading to 12α-hydroxy-3-oxo-4,6choldienoate (HOCDA, IX) as prominent intermediate.…”