Glycyl Radical Enzymes and Sulfonate Metabolism in the Microbiome

2021 ◽  
Vol 90 (1) ◽  
Author(s):  
Yifeng Wei ◽  
Yan Zhang
Keyword(s):  
Bond Cleavage ◽  
Anaerobic Bacteria ◽  
Sulfur Cycle ◽  
Annual Review ◽  
Publication Date ◽  
Strictly Anaerobic ◽  
Glycyl Radical ◽  
Free Radical Chemistry ◽  
Reducing Bacteria ◽  
Radical Enzymes

Sulfonates include diverse natural products and anthropogenic chemicals and are widespread in the environment. Many bacteria can degrade sulfonates and obtain sulfur, carbon, and energy for growth, playing important roles in the biogeochemical sulfur cycle. Cleavage of the inert sulfonate C–S bond involves a variety of enzymes, cofactors, and oxygen-dependent and oxygen-independent catalytic mechanisms. Sulfonate degradation by strictly anaerobic bacteria was recently found to involve C–S bond cleavage through O2-sensitive free radical chemistry, catalyzed by glycyl radical enzymes (GREs). The associated discoveries of new enzymes and metabolic pathways for sulfonate metabolism in diverse anaerobic bacteria have enriched our understanding of sulfonate chemistry in the anaerobic biosphere. An anaerobic environment of particular interest is the human gut microbiome, where sulfonate degradation by sulfate- and sulfite-reducing bacteria (SSRB) produces H2S, a process linked to certain chronic diseases and conditions. Expected final online publication date for the Annual Review of Biochemistry, Volume 90 is June 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals Two radical-dependent mechanisms for anaerobic degradation of the globally abundant organosulfur compound dihydroxypropanesulfonate

2020 ◽  
Vol 117 (27) ◽  
pp. 15599-15608 ◽  
Author(s):  
Jiayi Liu ◽  
Yifeng Wei ◽  
Lianyun Lin ◽  
Lin Teng ◽  
Jinyu Yin ◽  
...  
Keyword(s):  
Anaerobic Degradation ◽  
Organosulfur Compound ◽  
Sulfur Cycle ◽  
Marine Phytoplankton ◽  
Human Gut ◽  
Terminal Electron Acceptor ◽  
Glycyl Radical ◽  
Fermenting Bacteria ◽  
Reducing Bacteria

2(S)-dihydroxypropanesulfonate (DHPS) is a microbial degradation product of 6-deoxy-6-sulfo-d-glucopyranose (sulfoquinovose), a component of plant sulfolipid with an estimated annual production of 1010tons. DHPS is also at millimolar levels in highly abundant marine phytoplankton. Its degradation and sulfur recycling by microbes, thus, play important roles in the biogeochemical sulfur cycle. However, DHPS degradative pathways in the anaerobic biosphere are not well understood. Here, we report the discovery and characterization of two O2-sensitive glycyl radical enzymes that use distinct mechanisms for DHPS degradation. DHPS-sulfolyase (HpsG) in sulfate- and sulfite-reducing bacteria catalyzes C–S cleavage to release sulfite for use as a terminal electron acceptor in respiration, producing H2S. DHPS-dehydratase (HpfG), in fermenting bacteria, catalyzes C–O cleavage to generate 3-sulfopropionaldehyde, subsequently reduced by the NADH-dependent sulfopropionaldehyde reductase (HpfD). Both enzymes are present in bacteria from diverse environments including human gut, suggesting the contribution of enzymatic radical chemistry to sulfur flux in various anaerobic niches.

scholarly journals Energy Conservation in Fermentations of Anaerobic Bacteria

2021 ◽  
Vol 12 ◽  
Author(s):  
Wolfgang Buckel
Keyword(s):  
Anaerobic Bacteria ◽  
Human Microbiome ◽  
Oxidative Decarboxylation ◽  
Free Energies ◽  
Glutamate Mutase ◽  
Available Energy ◽  
Glycyl Radical ◽  
Oxygen Sensitive ◽  
Coenzyme B ◽  
Radical Enzymes

Anaerobic bacteria ferment carbohydrates and amino acids to obtain energy for growth. Due to the absence of oxygen and other inorganic electron acceptors, the substrate of a fermentation has to serve as electron donor as well as acceptor, which results in low free energies as compared to that of aerobic oxidations. Until about 10 years ago, anaerobes were thought to exclusively use substrate level phosphorylation (SLP), by which only part of the available energy could be conserved. Therefore, anaerobes were regarded as unproductive and inefficient energy conservers. The discovery of electrochemical Na+ gradients generated by biotin-dependent decarboxylations or by reduction of NAD+ with ferredoxin changed this view. Reduced ferredoxin is provided by oxidative decarboxylation of 2-oxoacids and the recently discovered flavin based electron bifurcation (FBEB). In this review, the two different fermentation pathways of glutamate to ammonia, CO2, acetate, butyrate and H2 via 3-methylaspartate or via 2-hydroxyglutarate by members of the Firmicutes are discussed as prototypical examples in which all processes characteristic for fermentations occur. Though the fermentations proceed on two entirely different pathways, the maximum theoretical amount of ATP is conserved in each pathway. The occurrence of the 3-methylaspartate pathway in clostridia from soil and the 2-hydroxyglutarate pathway in the human microbiome of the large intestine is traced back to the oxygen-sensitivity of the radical enzymes. The coenzyme B12-dependent glutamate mutase in the 3-methylaspartate pathway tolerates oxygen, whereas 2-hydroxyglutaryl-CoA dehydratase is extremely oxygen-sensitive and can only survive in the gut, where the combustion of butyrate produced by the microbiome consumes the oxygen and provides a strict anaerobic environment. Examples of coenzyme B12-dependent eliminases are given, which in the gut are replaced by simpler extremely oxygen sensitive glycyl radical enzymes.

Metabolism of Hydrocarbons in n-Alkane-Utilizing Anaerobic Bacteria

2016 ◽  
Vol 26 (1-3) ◽  
pp. 138-151 ◽  
Author(s):  
Heinz Wilkes ◽  
Wolfgang Buckel ◽  
Bernard T. Golding ◽  
Ralf Rabus
Keyword(s):  
Bond Cleavage ◽  
Anaerobic Bacteria ◽  
Sulfate Reducer ◽  
Alkane Degradation ◽  
Carbon Centers ◽  
Glycyl Radical ◽  
Kinetic Isotope ◽  
Dead End ◽  
Bacterium Strain ◽  
Glycyl Radical Enzyme

The glycyl radical enzyme-catalyzed addition of <i>n</i>-alkanes to fumarate creates a C-C-bond between two concomitantly formed stereogenic carbon centers. The configurations of the two diastereoisomers of the product resulting from <i>n</i>-hexane activation by the <i>n</i>-alkane-utilizing denitrifying bacterium strain HxN1, i.e. (1-methylpentyl)succinate, were assigned as (2<i>S</i>,1′<i>R</i>) and (2<i>R</i>,1′<i>R</i>). Experiments with stereospecifically deuterated <i>n</i>-(2,5-<sup>2</sup>H<sub>2</sub>)hexanes revealed that exclusively the pro-<i>S</i> hydrogen atom is abstracted from C2 of the <i>n</i>-alkane by the enzyme and later transferred back to C3 of the alkylsuccinate formed. These results indicate that the alkylsuccinate-forming reaction proceeds with an inversion of configuration at the carbon atom (C2) of the <i>n</i>-alkane forming the new C-C-bond, and thus stereochemically resembles a S<sub>N</sub>2-type reaction. Therefore, the reaction may occur in a concerted manner, which may avoid the highly energetic hex-2-yl radical as an intermediate. The reaction is associated with a significant primary kinetic isotope effect (kH/kD ≥3) for hydrogen, indicating that the homolytic C-H-bond cleavage is involved in the first irreversible step of the reaction mechanism. The (1-methylalkyl)succinate synthases of <i>n</i>-alkane-utilizing anaerobic bacteria apparently have very broad substrate ranges enabling them to activate not only aliphatic but also alkyl-aromatic hydrocarbons. Thus, two denitrifiers and one sulfate reducer were shown to convert the nongrowth substrate toluene to benzylsuccinate and further to the dead-end product benzoyl-CoA. For this purpose, however, the modified β-oxidation pathway known from alkylbenzene-utilizing bacteria was not employed, but rather the pathway used for <i>n</i>-alkane degradation involving CoA ligation, carbon skeleton rearrangement and decarboxylation. Furthermore, various <i>n</i>-alkane- and alkylbenzene-utilizing denitrifiers and sulfate reducers were found to be capable of forming benzyl alcohols from diverse alkylbenzenes, putatively via dehydrogenases. The thermophilic sulfate reducer strain TD3 forms <i>n</i>-alkylsuccinates during growth with <i>n</i>-alkanes or crude oil, which, based on the observed patterns of homologs, do not derive from a terminal activation of <i>n</i>-alkanes.

Predictive Platforms of Bond Cleavage and Drug Release Kinetics for Macromolecule–Drug Conjugates

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Souvik Ghosal ◽  
Javon E. Walker ◽  
Christopher A. Alabi
Keyword(s):  
Drug Release ◽  
Bond Cleavage ◽  
Release Kinetics ◽  
Therapeutic Index ◽  
Annual Review ◽  
Publication Date ◽  
Release Kinetic ◽  
Drug Release Kinetics ◽  
Drug Conjugates ◽  
Target Drug

Macromolecule–drug conjugates (MDCs) occupy a critical niche in modern pharmaceuticals that deals with the assembly and combination of a macromolecular carrier, a drug cargo, and a linker toward the creation of effective therapeutics. Macromolecular carriers such as synthetic biocompatible polymers and proteins are often exploited for their inherent ability to improve drug circulation, prevent off-target drug cytotoxicity, and widen the therapeutic index of drugs. One of the most significant challenges in MDC design involves tuning their drug release kinetics to achieve high spatiotemporal precision. This level of control requires a thorough qualitative and quantitative understanding of the bond cleavage event. In this review, we highlight specific research findings that emphasize the importance of establishing a precise structure–function relationship for MDCs that can be used to predict their bond cleavage and drug release kinetic parameters. Expected final online publication date for the Annual Review of Chemical and Biomolecular Engineering, Volume 12 is June 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

New glycyl radical enzymes catalysing key metabolic steps in anaerobic bacteria

2005 ◽  
Vol 386 (10) ◽  
Author(s):  
Thorsten Selmer ◽  
Antonio J. Pierik ◽  
Johann Heider
Keyword(s):  
Anaerobic Bacteria ◽  
Glycyl Radical ◽  
Radical Enzymes

scholarly journals Sulfidogenesis from 2-Aminoethanesulfonate (Taurine) Fermentation by a Morphologically Unusual Sulfate-Reducing Bacterium,Desulforhopalus singaporensis sp. nov

1999 ◽  
Vol 65 (8) ◽  
pp. 3328-3334 ◽  
Author(s):  
Thomas J. Lie ◽  
Michael L. Clawson ◽  
Walter Godchaux ◽  
Edward R. Leadbetter
Keyword(s):  
Marine Bacterium ◽  
Enrichment Culture ◽  
Bond Cleavage ◽  
Sole Source ◽  
Sulfur Cycle ◽  
Terminal Electron Acceptor ◽  
Sulfate Reducing ◽  
16S Ribosomal Dna ◽  
End Products ◽  
Reducing Bacteria

ABSTRACT A pure culture of an obligately anaerobic marine bacterium was obtained from an anaerobic enrichment culture in which taurine (2-aminoethanesulfonate) was the sole source of carbon, energy, and nitrogen. Taurine fermentation resulted in acetate, ammonia, and sulfide as end products. Other sulfonates, including 2-hydroxyethanesulfonate (isethionate) and cysteate (alanine-3-sulfonate), were not fermented. When malate was the sole source of carbon and energy, the bacterium reduced sulfate, sulfite, thiosulfate, or nitrate (reduced to ammonia) but did not use fumarate or dimethyl sulfoxide as a terminal electron acceptor for growth. Taurine-grown cells had significantly lower adenylylphosphosulfate reductase activities than sulfate-grown cells had, which was consistent with the notion that sulfate was not released as a result of oxidative C-S bond cleavage and then assimilated. The name Desulforhopalus singaporensis is proposed for this sulfate-reducing bacterium, which is morphologically unusual compared to the previously described sulfate-reducing bacteria by virtue of the spinae present on the rod-shaped, gram-negative, nonmotile cells; endospore formation was not discerned, nor was desulfoviridin detected. Granules of poly-β-hydroxybutyrate were abundant in taurine-grown cells. This organism shares with the other member of the genusDesulforhopalus which has been described a unique 13-base deletion in the 16S ribosomal DNA. It differs in several ways from a recently described endospore-forming anaerobe (K. Denger, H. Laue, and A. M. Cook, Arch. Microbiol. 168:297–301, 1997) that reportedly produces thiosulfate but not sulfide from taurine fermentation.D. singaporensis thus appears to be the first example of an organism which exhibits sulfidogenesis during taurine fermentation. Implications for sulfonate sulfur in the sulfur cycle are discussed.

Endogenous Retroviruses Drive Resistance and Promotion of Exogenous Retroviral Homologs

2020 ◽  
Vol 9 (1) ◽  
Author(s):  
Elliott S. Chiu ◽  
Sue VandeWoude
Keyword(s):  
Immune Modulation ◽  
Viral Infections ◽  
Viral Evolution ◽  
Endogenous Retroviruses ◽  
Annual Review ◽  
Publication Date ◽  
Biological Functions ◽  
Self Tolerance ◽  
Vertebrate Hosts ◽  
Insight Into

Endogenous retroviruses (ERVs) serve as markers of ancient viral infections and provide invaluable insight into host and viral evolution. ERVs have been exapted to assist in performing basic biological functions, including placentation, immune modulation, and oncogenesis. A subset of ERVs share high nucleotide similarity to circulating horizontally transmitted exogenous retrovirus (XRV) progenitors. In these cases, ERV–XRV interactions have been documented and include ( a) recombination to result in ERV–XRV chimeras, ( b) ERV induction of immune self-tolerance to XRV antigens, ( c) ERV antigen interference with XRV receptor binding, and ( d) interactions resulting in both enhancement and restriction of XRV infections. Whereas the mechanisms governing recombination and immune self-tolerance have been partially determined, enhancement and restriction of XRV infection are virus specific and only partially understood. This review summarizes interactions between six unique ERV–XRV pairs, highlighting important ERV biological functions and potential evolutionary histories in vertebrate hosts. Expected final online publication date for the Annual Review of Animal Biosciences, Volume 9 is February 16, 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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