Bacterial Steroid Catabolism

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Microbial Biotechnology".

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 17645

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Guest Editor
Department of Molecular Biology, Veterinary Faculty, Campus de Vegazana, Universidad de León, 24007 León, Spain
Interests: microbiology; biotechnology; biodegradation; steroids; polyhydroxyalkanoates; aromatic compounds; polyethylene terephthalate; biogenic amines; polyamines
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Special Issue Information

Dear Colleagues,

Steroid compounds are almost exclusively produced by eukaryotic organisms, where they fulfill various biological functions, such as serving as membrane components (e.g., cholesterol, ergosterol, and phytosterols), allowing fat absorption during digestion (bile acids), or acting as hormones (e.g., testosterone and estradiol). The presence of these compounds in the environment has recently increased due to their discharge by urban effluents and the increase in livestock farms. Once these compounds are released to the environment, they can undergo different modifications, originating molecules with endocrine modulation potential. Thus, one of the major concerns about these compounds is their ability to alter the sexual behavior and endocrine systems of wildlife. Because of the negative environmental impacts of steroid compounds, their removal from the environment by microorganisms has attracted increasing interest.

Additionally, the potential use of these microorganisms, or at least some of their metabolic functions, in the pharmaceutical industry for the production of syntones, hormones, or semisynthetic derivatives of these, have focused the interest in the knowledge of the metabolic determinants and the pathways used by microorganisms to catabolize or modify these steroid compounds.

Accordingly, different metabolic strategies adopted by bacteria for the use of steroid compounds have been recently documented. Thus, the characterization of the 9,10-seco pathway for the degradation of sterols, testosterone, bile acids, and related compounds by different Actinobacteria (e.g., different strains of Mycobacterium, Rhodococcus, and Gordonia) as well as some Gram-negative bacteria (e.g., Comamonas, Pseudomonas) has been documented. For the degradation of estrogens, a novel strategy—the so-called 4,5-seco pathway—has been proposed. Furthermore, the anaerobic metabolism of sterols by strains belonging to the genera Sterolibacterium and Steroidobacter through the 2,3-seco pathway has been also observed.

This Special Issue of Microorganisms aims to present the current research on steroid degradation, to show a deeper characterization of the known pathways, to describe the presence and characteristics of these pathways in new organisms, and to propose new metabolic strategies for the degradation of this class of compounds. Biotechnological applications derived from knowledge of microbial degradative pathways are also welcome. We would also consider chemotoxicological or ecological studies on how the spillage of these compounds affects the composition of natural microbiomes in different niches.

We deeply encourage and appreciate your participation in this Special Issue.

Prof. Elías R. Olivera
Guest Editor

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Keywords

  • steroids
  • sterols
  • testosterone
  • bile acids
  • estrogens
  • Mycobacterium
  • Rhodococcus
  • Gordonia
  • Novosphingobium
  • Comamonas
  • Pseudomonas
  • 9,10-seco pathway
  • 2,3-seco pathway
  • 4,5-seco pathway
  • ecological impact

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Published Papers (4 papers)

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Research

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19 pages, 3402 KiB  
Article
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
by Franziska Maria Feller, Sebastian Eilebrecht, Ruslan Nedielkov, Onur Yücel, Julia Alvincz, Gabriela Salinas, Kevin Christopher Ludwig, Heiko Möller and Bodo Philipp
Microorganisms 2021, 9(10), 2146; https://doi.org/10.3390/microorganisms9102146 - 14 Oct 2021
Cited by 1 | Viewed by 2385
Abstract
Bile salts such as cholate are steroid compounds from the digestive tracts of vertebrates, which enter the environment upon excretion, e.g., in manure. Environmental bacteria degrade bile salts aerobically via two pathway variants involving intermediates with Δ1,4- or Δ4,6-3-keto-structures [...] Read more.
Bile salts such as cholate are steroid compounds from the digestive tracts of vertebrates, which enter the environment upon excretion, e.g., in manure. Environmental bacteria degrade bile salts aerobically via two pathway variants involving intermediates with Δ1,4- or Δ4,6-3-keto-structures of the steroid skeleton. Recent studies indicated that degradation of bile salts via Δ4,6-3-keto intermediates in Sphingobium sp. strain Chol11 proceeds via 9,10-seco cleavage of the steroid skeleton. For further elucidation, the presumptive product of this cleavage, 3,12β-dihydroxy-9,10-seco-androsta-1,3,5(10),6-tetraene-9,17-dione (DHSATD), was provided to strain Chol11 in a co-culture approach with Pseudomonas stutzeri Chol1 and as purified substrate. Strain Chol11 converted DHSATD to the so far unknown compound 4-methyl-3-deoxy-1,9,12-trihydroxyestra-1,3,5(10)7-tetraene-6,17-dione (MDTETD), presumably in a side reaction involving an unusual ring closure. MDTETD was neither degraded by strains Chol1 and Chol11 nor in enrichment cultures. Functional transcriptome profiling of zebrafish embryos after exposure to MDTETD identified a significant overrepresentation of genes linked to hormone responses. In both pathway variants, steroid degradation intermediates transiently accumulate in supernatants of laboratory cultures. Soil slurry experiments indicated that bacteria using both pathway variants were active and also released their respective intermediates into the environment. This instance could enable the formation of recalcitrant steroid metabolites by interspecies cross-feeding in agricultural soils. Full article
(This article belongs to the Special Issue Bacterial Steroid Catabolism)
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13 pages, 2379 KiB  
Article
Engineering the Steroid Hydroxylating System from Cochliobolus lunatus in Mycolicibacterium smegmatis
by Carmen Felpeto-Santero, Beatriz Galán and José Luis García
Microorganisms 2021, 9(7), 1499; https://doi.org/10.3390/microorganisms9071499 - 13 Jul 2021
Cited by 9 | Viewed by 3178
Abstract
14α-hydroxylated steroids are starting materials for the synthesis of contraceptive and anti-inflammatory compounds in the steroid industry. A synthetic bacterial operon containing the cytochrome P450 CYP103168 and the reductase CPR64795 of the fungus Cochlioboluslunatus able to hydroxylate steroids has been engineered into [...] Read more.
14α-hydroxylated steroids are starting materials for the synthesis of contraceptive and anti-inflammatory compounds in the steroid industry. A synthetic bacterial operon containing the cytochrome P450 CYP103168 and the reductase CPR64795 of the fungus Cochlioboluslunatus able to hydroxylate steroids has been engineered into a shuttle plasmid named pMVFAN. This plasmid was used to transform two mutants of Mycolicibacterium smegmatis named MS6039-5941 and MS6039 that accumulate 4-androstene-3,17-dione (AD), and 1,4-androstadiene-3,17-dione (ADD), respectively. The recombinant mutants MS6039-5941 (pMVFAN) and MS6039 (pMVFAN) were able to efficiently express the hydroxylating CYP system of C.lunatus and produced in high yields 14αOH-AD and 14αOH-ADD, respectively, directly from cholesterol and phytosterols in a single fermentation step. These results open a new avenue for producing at industrial scale these and other hydroxylated steroidal synthons by transforming with this synthetic operon other Mycolicibacterium strains currently used for the commercial production of steroidal synthons from phytosterols as feedstock. Full article
(This article belongs to the Special Issue Bacterial Steroid Catabolism)
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19 pages, 3206 KiB  
Article
Further Studies on the 3-Ketosteroid 9α-Hydroxylase of Rhodococcus ruber Chol-4, a Rieske Oxygenase of the Steroid Degradation Pathway
by Sara Baldanta, Juana María Navarro Llorens and Govinda Guevara
Microorganisms 2021, 9(6), 1171; https://doi.org/10.3390/microorganisms9061171 - 29 May 2021
Cited by 8 | Viewed by 2693
Abstract
The biochemistry and genetics of the bacterial steroid catabolism have been extensively studied during the last years and their findings have been essential to the development of biotechnological applications. For instance, metabolic engineering of the steroid-eater strains has allowed to obtain intermediaries of [...] Read more.
The biochemistry and genetics of the bacterial steroid catabolism have been extensively studied during the last years and their findings have been essential to the development of biotechnological applications. For instance, metabolic engineering of the steroid-eater strains has allowed to obtain intermediaries of industrial value. However, there are still some drawbacks that must be overcome, such as the redundancy of the steroid catabolism genes in the genome and a better knowledge of its genetic regulation. KshABs and KstDs are key enzymes involved in the aerobic breakage of the steroid nucleus. Rhodococcus ruber Chol-4 contains three kshAs genes, a single kshB gene and three kstDs genes within its genome. In the present work, the growth of R. ruber ΔkshA strains was evaluated on different steroids substrates; the promoter regions of these genes were analyzed; and their expression was followed by qRT-PCR in both wild type and ksh mutants. Additionally, the transcription level of the kstDs genes was studied in the ksh mutants. The results show that KshA2B and KshA1B are involved in AD metabolism, while KshA3B and KshA1B contribute to the cholesterol metabolism in R. ruber. In the kshA single mutants, expression of the remaining kshA and kstD genes is re-organized to survive on the steroid substrate. These data give insight into the fine regulation of steroid genes when several isoforms are present. Full article
(This article belongs to the Special Issue Bacterial Steroid Catabolism)
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Review

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12 pages, 482 KiB  
Review
Bile Salt Hydrolases: At the Crossroads of Microbiota and Human Health
by Mélanie Bourgin, Aicha Kriaa, Héla Mkaouar, Vincent Mariaule, Amin Jablaoui, Emmanuelle Maguin and Moez Rhimi
Microorganisms 2021, 9(6), 1122; https://doi.org/10.3390/microorganisms9061122 - 22 May 2021
Cited by 55 | Viewed by 8633
Abstract
The gut microbiota has been increasingly linked to metabolic health and disease over the last few decades. Several factors have been suggested to be involved in lipid metabolism and metabolic responses. One mediator that has gained great interest as a clinically important enzyme [...] Read more.
The gut microbiota has been increasingly linked to metabolic health and disease over the last few decades. Several factors have been suggested to be involved in lipid metabolism and metabolic responses. One mediator that has gained great interest as a clinically important enzyme is bile salt hydrolase (BSH). BSH enzymes are widely distributed in human gastrointestinal microbial communities and are believed to play key roles in both microbial and host physiology. In this review, we discuss the current evidence related to the role of BSHs in health and provide useful insights that may pave the way for new therapeutic targets in human diseases. Full article
(This article belongs to the Special Issue Bacterial Steroid Catabolism)
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