scholarly journals Steroid Metabolism In Thermophilic Actinobacteria Saccharopolyspora Hirsuta Subsp. Hirsuta VKM Ac-666T

2021 ◽  
Author(s):  
Tatyana Gennadyevna Lobastova ◽  
Victoria V. Fokina ◽  
Sergey V. Tarlachkov ◽  
Andrey A. Shutov ◽  
Eugeny Yu. Bragin ◽  
...  
Keyword(s):  
Structural Modification ◽  
Thermophilic Bacteria ◽  
Cholesterol Oxidase ◽  
Bioinformatic Analysis ◽  
Degradation Pathway ◽  
Side Chain ◽  
P450 Monooxygenase ◽  
Key Genes ◽  
Saccharopolyspora Hirsuta ◽  
Steroid Catabolism

Abstract Application of thermophile microorganisms opens new prospects in steroid biotechnology, however little is known on steroid catabolism by the thermophile strains.The thermophilic Saccharopolyspora hirsuta subsp. hirsuta strain VKM Ac-666T is capable of structural modification of different steroids, and fully degrades cholesterol. The intermediates of the cholesterol degradation pathway were identified as cholest-4-en-3-one, cholesta-1,4-dien-3-one, 26-hydroxycholest-4-en-3-one, 3-oxo-cholest-4-en-26-oic acid, 3-oxo-cholesta-1,4-dien-26-oic acid, 26-hydroxycholesterol, 3β-hydroxy-cholest-5-en-26-oic acid by MS, and H1- and C13-NMR analyses. The data evidence sterol degradation by the strain occurs simultaneously through the aliphatic side chain hydroxylation at C26 and the A-ring modification that are putatively catalyzed by cytochrome P450 monooxygenase CYP125 and cholesterol oxidase, respectively.The genes orthologous to those related to the sterol side chain degradation, steroid core rings A/B and C/D disruption and the steroid uptake were revealed. Most of the genes related to steroid degradation are grouped in three clusters. The sets of the genes putatively involved in steroid catabolism and peculiarities of their organization in S. hirsuta are discussed.Despite steroids abundancy in the environments, the ability to degrade them is not widespread among thermophilic bacteria as follows from the bioinformatic analysis of 52 publicly available genomes. Only seven candidate strains were revealed to possess the key genes related to the only known 9(10)-seco pathway of steroid degradation.The results contribute to the knowledge on diversity of microbial steroid degraders, the features of sterol catabolism by thermophilic actinobacteria and could be useful for application in the pharmaceutical and environmental biotechnology.

scholarly journals Steroid Metabolism in Thermophilic Actinobacterium Saccharopolyspora hirsuta VKM Ac-666T

2021 ◽  
Vol 9 (12) ◽  
pp. 2554
Author(s):  
Tatyana Lobastova ◽  
Victoria Fokina ◽  
Sergey Tarlachkov ◽  
Andrey Shutov ◽  
Eugeny Bragin ◽  
...  
Keyword(s):  
Thermophilic Bacteria ◽  
Cholesterol Oxidase ◽  
Cascade Reactions ◽  
Cholesterol Oxidation ◽  
P450 Monooxygenase ◽  
Thermophilic Microorganisms ◽  
Mycobacterium Tuberculosis H37rv ◽  
Rhodococcus Jostii Rha1 ◽  
Saccharopolyspora Hirsuta ◽  
Steroid Catabolism

The application of thermophilic microorganisms opens new prospects in steroid biotechnology, but little is known to date on steroid catabolism by thermophilic strains. The thermophilic strain Saccharopolyspora hirsuta VKM Ac-666T has been shown to convert various steroids and to fully degrade cholesterol. Cholest-4-en-3-one, cholesta-1,4-dien-3-one, 26-hydroxycholest-4-en-3-one, 3-oxo-cholest-4-en-26-oic acid, 3-oxo-cholesta-1,4-dien-26-oic acid, 26-hydroxycholesterol, 3β-hydroxy-cholest-5-en-26-oic acid were identified as intermediates in cholesterol oxidation. The structures were confirmed by 1H and 13C-NMR analyses. Aliphatic side chain hydroxylation at C26 and the A-ring modification at C3, which are putatively catalyzed by cytochrome P450 monooxygenase CYP125 and cholesterol oxidase, respectively, occur simultaneously in the strain and are followed by cascade reactions of aliphatic sidechain degradation and steroid core destruction via the known 9(10)-seco-pathway. The genes putatively related to the sterol and bile acid degradation pathways form three major clusters in the S. hirsuta genome. The sets of the genes include the orthologs of those involved in steroid catabolism in Mycobacterium tuberculosis H37Rv and Rhodococcus jostii RHA1 and related actinobacteria. Bioinformatics analysis of 52 publicly available genomes of thermophilic bacteria revealed only seven candidate strains that possess the key genes related to the 9(10)-seco pathway of steroid degradation, thus demonstrating that the ability to degrade steroids is not widespread among thermophilic bacteria.

Corticosteroid Catabolism by Klebsiella pneumoniae as a Possible Mechanism for Increased Pneumonia Risk

2019 ◽  
Vol 20 (4) ◽  
pp. 309-316 ◽  
Author(s):  
Pritam Chattopadhyay ◽  
Goutam Banerjee
Keyword(s):  
Amino Acid ◽  
Klebsiella Pneumoniae ◽  
Kegg Pathway ◽  
Degradation Pathway ◽  
Amino Acid Sequences ◽  
Biological Mechanism ◽  
Clinical Strains ◽  
Catabolism Pathway ◽  
Steroid Catabolism ◽  
Nutrition Source

Background: Several strains of Klebsiella pneumoniae are responsible for causing pneumonia in lung and thereby causing death in immune-suppressed patients. In recent year, few investigations have reported the enhancement of K. pneumoniae population in patients using corticosteroid containing inhaler. Objectives: The biological mechanism(s) behind this increased incidence has not been elucidated. Therefore, the objective of this investigating was to explore the relation between Klebsiella pneumoniae and increment in carbapenamase producing Enterobacteriaceae score (ICS). Methods: The available genomes of K. pneumoniae and the amino acid sequences of steroid catabolism pathway enzymes were taken from NCBI database and KEGG pathway tagged with UniPort database, respectively. We have used different BLAST algorithms (tBLASTn, BLASTp, psiBLAST, and delBLAST) to identify enzymes (by their amino acid sequence) involved in steroid catabolism. Results: A total of 13 enzymes (taken from different bacterial candidates) responsible for corticosteroid degradation have been identified in the genome of K. pneumoniae. Finally, 8 enzymes (K. pneumoniae specific) were detected in four clinical strains of K. pneumoniae. This investigation intimates that this ability to catabolize corticosteroids could potentially be one mechanism behind the increased pneumonia incidence. Conclusion: The presence of corticosteroid catabolism enzymes in K. pneumoniae enhances the ability to utilize corticosteroid for their own nutrition source. This is the first report to demonstrate the corticosteroid degradation pathway in clinical strains of K. pneumoniae.

scholarly journals Further Studies on the 3-Ketosteroid 9α-Hydroxylase of Rhodococcus ruber Chol-4, a Rieske Oxygenase of the Steroid Degradation Pathway

2021 ◽  
Vol 9 (6) ◽  
pp. 1171
Author(s):  
Sara Baldanta ◽  
Juana María Navarro Llorens ◽  
Govinda Guevara
Keyword(s):  
Cholesterol Metabolism ◽  
Genetic Regulation ◽  
Degradation Pathway ◽  
Rhodococcus Ruber ◽  
Promoter Regions ◽  
Steroid Nucleus ◽  
Steroid Substrate ◽  
Fine Regulation ◽  
Rieske Oxygenase ◽  
Steroid Catabolism

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.

Critical Review of Biotransformational Studies on Steroids by Using Culture of Cunninghamella blakesleeana

2021 ◽  
Vol 18 ◽  
Author(s):  
Azizuddin ◽  
Muhammad Iqbal ◽  
Syed Ghulam Musharraf
Keyword(s):  
Double Bond ◽  
Critical Review ◽  
Structural Modification ◽  
Bond Formation ◽  
Environmentally Friendly ◽  
Side Chain ◽  
Synthetic Compounds ◽  
Efficient Approach ◽  
Cunninghamella Blakesleeana ◽  
Different Strains

: For several decades, biotransformational studies on steroidal compounds have gained a lot of attention because it is an efficient approach for the structural modification of complicated natural or synthetic compounds with high regio-, chemo- and stereoselectivity at environmentally friendly conditions. This review summarizes the use of different strains of Cunninghamella blakesleeana for the biotransformation of sixteen steroids 1-16 into a variety of transformed products. The transformed products may be important as a drug or precursor for the production of important pharmaceuticals. The types of reactions performed by C. blakesleeana include hydroxylation, epoxidation, reduction, demethylation, oxidation, glycosidation, double bond formation, side-chain degradation, isomerisation and opening of an isoxazol ring, which would be difficult to produce by traditional synthesis.

scholarly journals 7-Ketocholesterol Catabolism by Rhodococcus jostii RHA1

2009 ◽  
Vol 76 (1) ◽  
pp. 352-355 ◽  
Author(s):  
Jacques M. Mathieu ◽  
William W. Mohn ◽  
Lindsay D. Eltis ◽  
Justin C. LeBlanc ◽  
Gord R. Stewart ◽  
...  
Keyword(s):  
Differentially Expressed Genes ◽  
Gene Clusters ◽  
Differentially Expressed ◽  
Large Gene ◽  
Key Genes ◽  
Rhodococcus Jostii Rha1 ◽  
Harmful Effects ◽  
Steroid Catabolism ◽  
Rhodococcus Jostii

ABSTRACT Oxysterols from steroid autooxidation have numerous harmful effects, but their biodegradation is poorly understood. Microarrays were used to study mineralization of the most common oxysterol, 7-ketocholesterol (7KC), by Rhodococcus jostii RHA1. Growth on 7KC versus growth on cholesterol resulted in 363 differentially expressed genes, including upregulation of two large gene clusters putatively encoding steroid catabolism. Despite this difference, 7KC degradation required key genes involved in cholesterol degradation, indicating a common catabolic route.

scholarly journals P450 monooxygenase ComJ catalyses side chain phenolic cross-coupling during complestatin biosynthesis

RSC Advances ◽  
2017 ◽  
Vol 7 (56) ◽  
pp. 35376-35384 ◽  
Author(s):  
Aurelio Mollo ◽  
A. Nikolai von Krusenstiern ◽  
Joshua A. Bulos ◽  
Veronika Ulrich ◽  
Karin S. Åkerfeldt ◽  
...  
Keyword(s):  
High Efficiency ◽  
Bond Formation ◽  
Cross Coupling ◽  
Side Chain ◽  
P450 Monooxygenase ◽  
Peptide Substrates ◽  
Ether Bond ◽  
Biaryl Ether

P450 monooxygenase enzyme ComJ catalyzed biaryl ether bond formation with high efficiency and low stereoselectivity on selected complestatin-like peptide substrates.

scholarly journals Structure-guided function discovery of an NRPS-like glycine betaine reductase for choline biosynthesis in fungi

2019 ◽  
Author(s):  
Yang Hai ◽  
Arthur Huang ◽  
Yi Tang
Keyword(s):  
Glycine Betaine ◽  
Genome Mining ◽  
Domain Architecture ◽  
Homology Model ◽  
Bioinformatic Analysis ◽  
Degradation Pathway ◽  
Substrate Analogs ◽  
Peptide Synthetases ◽  
Primary And Secondary Metabolism ◽  
Function Discovery

ABSTRACTNonribosomal peptide synthetases (NRPS) and NRPS-like enzymes have diverse functions in primary and secondary metabolism. By using a structure-guided approach, we uncovered the function of an NRPS-like enzyme with unusual domain architecture, catalyzing two sequential two-electron reductions of glycine betaine to choline. Structural analysis based on homology model suggests cation-π interactions as the major substrate specificity determinant, which was verified using substrate analogs and inhibitors. Bioinformatic analysis indicates this NRPS-like glycine betaine reductase is highly conserved and widespread in fungi kingdom. Genetic knockout experiments confirmed its role in choline biosynthesis and maintaining glycine betaine homeostasis in fungi. Our findings demonstrate that the oxidative choline-glycine betaine degradation pathway can operate in a fully reversible fashion and provide new insights in understanding fungal choline metabolism. The use of an NRPS-like enzyme for reductive choline formation is energetically efficient compared to known pathways. Our discovery also underscores the capabilities of structure-guided approach in assigning function of uncharacterized multidomain proteins, which can potentially aid functional discovery of new enzymes by genome mining.

Sign in / Sign up

Export Citation Format

Share Document