scholarly journals Anaerobic 4‐Hydroxyproline Metabolism by a Widespread Microbial Glycyl Radical Enzyme

2018 ◽  
Vol 32 (S1) ◽  
Author(s):  
Yolanda Y. Huang ◽  
Lindsey Backman ◽  
Brian Gold ◽  
Ronald T. Raines ◽  
Catherine L. Drennan ◽  
...  
Keyword(s):  
Glycyl Radical ◽  
Hydroxyproline Metabolism ◽  
Glycyl Radical Enzyme

scholarly journals The Stickland fermentation precursor trans-4-hydroxyproline differentially impacts the metabolism of Clostridioides difficile and commensal Clostridia

2021 ◽  
Author(s):  
Casey M Theriot ◽  
Amber D Reed ◽  
Joshua R Fletcher ◽  
Yue (Yolanda) Huang ◽  
Rajani Thanissery ◽  
...  
Keyword(s):  
Amino Acid ◽  
Gut Microbiota ◽  
Clostridioides Difficile ◽  
Glycyl Radical ◽  
Metabolic Gene Expression ◽  
Hydroxyproline Metabolism ◽  
Mouse Model Of Infection ◽  
Glycyl Radical Enzyme ◽  
Significant Disease

An intact gut microbiota confers colonization resistance against Clostridioides difficile through a variety of mechanisms, likely including competition for nutrients. Recently, proline was identified as an important environmental amino acid that C. difficile uses to support growth and cause significant disease. The ability to dehydrate trans-4-hydroxyproline via the HypD glycyl radical enzyme is widespread amongst gut microbiota, including C. difficile and members of the commensal Clostridia, suggesting that this amino acid is an important nutrient in the host environment. Therefore, we constructed a C. difficile ΔhypD mutant and found that it was modestly impaired in fitness in a mouse model of infection, and was associated with an altered microbiota when compared to mice challenged with the wild type strain. Changes in the microbiota between the two groups were largely driven by members of the Lachnospiraceae family and the Clostridium genus. We found that C. difficile and type strains of three commensal Clostridia had significant alterations to their metabolic gene expression in the presence of trans-4-hydroxyproline in vitro. The proline reductase (prd) genes were elevated in C. difficile, consistent with the hypothesis that trans-4-hydroxyproline is used by C. difficile to supply proline for fermentation. Similar transcripts were also elevated in some commensal Clostridia tested, although each strain responded differently. This suggests that the uptake and utilization of other nutrients by the commensal Clostridia may be affected by trans-4-hydroxyproline metabolism, highlighting how a common nutrient may be a signal to each organism to adapt to a unique niche.

4-Hydroxyphenylacetate Decarboxylases:  Properties of a Novel Subclass of Glycyl Radical Enzyme Systems†

Biochemistry ◽  
2006 ◽  
Vol 45 (31) ◽  
pp. 9584-9592 ◽  
Author(s):  
Lihua Yu ◽  
Martin Blaser ◽  
Paula I. Andrei ◽  
Antonio J. Pierik ◽  
Thorsten Selmer
Keyword(s):  
Glycyl Radical ◽  
Enzyme Systems ◽  
Glycyl Radical Enzyme

scholarly journals Stable Isotope Fractionation Caused by Glycyl Radical Enzymes during Bacterial Degradation of Aromatic Compounds

2004 ◽  
Vol 70 (5) ◽  
pp. 2935-2940 ◽  
Author(s):  
Barbara Morasch ◽  
Hans H. Richnow ◽  
Andrea Vieth ◽  
Bernhard Schink ◽  
Rainer U. Meckenstock
Keyword(s):  
Stable Isotope ◽  
Carbon Isotope ◽  
Isotope Fractionation ◽  
Toluene Degradation ◽  
Fractionation Factor ◽  
Glycyl Radical ◽  
Stable Isotope Fractionation ◽  
Benzylsuccinate Synthase ◽  
Glycyl Radical Enzyme

ABSTRACT Stable isotope fractionation was studied during the degradation of m-xylene, o-xylene, m-cresol, and p-cresol with two pure cultures of sulfate-reducing bacteria. Degradation of all four compounds is initiated by a fumarate addition reaction by a glycyl radical enzyme, analogous to the well-studied benzylsuccinate synthase reaction in toluene degradation. The extent of stable carbon isotope fractionation caused by these radical-type reactions was between enrichment factors (ε) of −1.5 and −3.9, which is in the same order of magnitude as data provided before for anaerobic toluene degradation. Based on our results, an analysis of isotope fractionation should be applicable for the evaluation of in situ bioremediation of all contaminants degraded by glycyl radical enzyme mechanisms that are smaller than 14 carbon atoms. In order to compare carbon isotope fractionations upon the degradation of various substrates whose numbers of carbon atoms differ, intrinsic ε (εintrinsic) were calculated. A comparison of εintrinsic at the single carbon atoms of the molecule where the benzylsuccinate synthase reaction took place with compound-specific ε elucidated that both varied on average to the same extent. Despite variations during the degradation of different substrates, the range of ε found for glycyl radical reactions was reasonably narrow to propose that rough estimates of biodegradation in situ might be given by using an average ε if no fractionation factor is available for single compounds.

Crystal Structure of a Glycyl Radical Enzyme from Archaeoglobus fulgidus

2006 ◽  
Vol 357 (1) ◽  
pp. 221-235 ◽  
Author(s):  
Lari Lehtiö ◽  
J. Günter Grossmann ◽  
Bashkim Kokona ◽  
Robert Fairman ◽  
Adrian Goldman
Keyword(s):  
Crystal Structure ◽  
Archaeoglobus Fulgidus ◽  
Glycyl Radical ◽  
Glycyl Radical Enzyme

scholarly journals Glycyl Radical Enzyme-Associated Microcompartments: Redox-Replete Bacterial Organelles

mBio ◽  
2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Bryan Ferlez ◽  
Markus Sutter ◽  
Cheryl A. Kerfeld
Keyword(s):  
Substrate Specificity ◽  
Pathogenic Bacteria ◽  
External Source ◽  
Redox Proteins ◽  
Physiological Importance ◽  
Bacterial Microcompartments ◽  
Glycyl Radical ◽  
Self Assembling ◽  
Glycyl Radical Enzyme ◽  
Protein Shell

ABSTRACTAn increasing number of microbes are being identified that organize catabolic pathways within self-assembling proteinaceous structures known as bacterial microcompartments (BMCs). Most BMCs are characterized by their singular substrate specificity and commonly employ B12-dependent radical mechanisms. In contrast, a less-well-known BMC type utilizes the B12-independent radical chemistry of glycyl radical enzymes (GREs). Unlike B12-dependent enzymes, GREs require an activating enzyme (AE) as well as an external source of electrons to generate an adenosyl radical and form their catalytic glycyl radical. Organisms encoding these glycyl radical enzyme-associated microcompartments (GRMs) confront the challenge of coordinating the activation and maintenance of their GREs with the assembly of a multienzyme core that is encapsulated in a protein shell. The GRMs appear to enlist redox proteins to either generate reductants internally or facilitate the transfer of electrons from the cytosol across the shell. Despite this relative complexity, GRMs are one of the most widespread types of BMC, with distinct subtypes to catabolize different substrates. Moreover, they are encoded by many prominent gut-associated and pathogenic bacteria. In this review, we will focus on the diversity, function, and physiological importance of GRMs, with particular attention given to their associated and enigmatic redox proteins.

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