Delineation of Steroid-Degrading Microorganisms through Comparative Genomic Analysis

Abstract

Steroids are ubiquitous in natural environments and are a significant growth substrate for microorganisms. Microbial steroid metabolism is also important for some pathogens and for biotechnical applications. This study delineated the distribution of aerobic steroid catabolism pathways among over 8,000 microorganisms whose genomes are available in the NCBI RefSeq database. Combined analysis of bacterial, archaeal, and fungal genomes with both hidden Markov models and reciprocal BLAST identified 265 putative steroid degraders within only Actinobacteria and Proteobacteria, which mainly originated from soil, eukaryotic host, and aquatic environments. These bacteria include members of 17 genera not previously known to contain steroid degraders. A pathway for cholesterol degradation was conserved in many actinobacterial genera, particularly in members of the Corynebacterineae, and a pathway for cholate degradation was conserved in members of the genus Rhodococcus. A pathway for testosterone and, sometimes, cholate degradation had a patchy distribution among Proteobacteria. The steroid degradation genes tended to occur within large gene clusters. Growth experiments confirmed bioinformatic predictions of steroid metabolism capacity in nine bacterial strains. The results indicate there was a single ancestral 9,10-seco-steroid degradation pathway. Gene duplication, likely in a progenitor of Rhodococcus, later gave rise to a cholate degradation pathway. Proteobacteria and additional Actinobacteria subsequently obtained a cholate degradation pathway via horizontal gene transfer, in some cases facilitated by plasmids. Catabolism of steroids appears to be an important component of the ecological niches of broad groups of Actinobacteria and individual species of Proteobacteria.

Catabolism of the Last Two Steroid Rings in Mycobacterium tuberculosis and Other Bacteria

“…Indeed, differences in the HIP catabolic gene cluster in diverse bacteria appear to reflect the different steroid-catabolizing capabilities of the strains. For example, in bacteria that catabolize cholate or other bile acids, the HIP catabolic gene cluster contains echA13 (RHA1_RS22405 in R. jostii RHA1) (1, 9, 10). A homolog of EchA20, EchA13 is proposed to remove the hydroxyl of 7β-OH HIP, generated from cholate degradation (10, 20), and is not present in M. tuberculosis , which does not degrade cholate.…”

“…In eukaryotes, they serve as critical components of cell membranes, as signaling molecules, and in mammals, they absorb dietary fat. However, the only known organisms that can catabolize steroids and utilize them as growth substrates are bacteria (1). Bacterial steroid catabolism can be either aerobic, as occurs in most mycolic acid-containing actinobacteria and some proteobacteria (1–3), or anaerobic, as in some proteobacteria (4).…”

“…However, the only known organisms that can catabolize steroids and utilize them as growth substrates are bacteria (1). Bacterial steroid catabolism can be either aerobic, as occurs in most mycolic acid-containing actinobacteria and some proteobacteria (1–3), or anaerobic, as in some proteobacteria (4). Aerobic catabolism has been studied for many decades, due in part to its potential to transform low-value steroids into high-value ones (5).…”

Prenatal androgen exposure causes hypertension and gut microbiota dysbiosis

“…The fecal microbiota of PNA animals contained higher abundance of bacteria commonly associated with steroid hormone synthesis, including bacteria from the families Nocardiaceae 120 and Clostridiaceae . 121 , 122 In addition, PNA animals have significantly increased abundance of fecal bacteria associated with cardiovascular function including cardiac muscle contraction, proximal tubule bicarbonate reclamation, and the renin-angiotensin (RAS) system.…”

Bacterial CYP154C8 catalyzes carbon‐carbon bond cleavage in steroids

“…Steroids are ubiquitous growth substrates for microorganisms, and bacterial hydroxylase plays an important role in the degradation of steroids [38]. The possibility of the formation of such products might be due to the C-C bond cleavage between C20 and C21.…”