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Applied Microbiology and Biotechnology Jan 2019Natural rubber (NR), poly(cis-1,4-isoprene), is used in an industrial scale for more than 100 years. Most of the NR-derived materials are released to the environment as... (Review)
Review
Natural rubber (NR), poly(cis-1,4-isoprene), is used in an industrial scale for more than 100 years. Most of the NR-derived materials are released to the environment as waste or by abrasion of small particles from our tires. Furthermore, compounds with isoprene units in their molecular structures are part of many biomolecules such as terpenoids and carotenoids. Therefore, it is not surprising that NR-degrading bacteria are widespread in nature. NR has one carbon-carbon double bond per isoprene unit and this functional group is the primary target of NR-cleaving enzymes, so-called rubber oxygenases. Rubber oxygenases are secreted by rubber-degrading bacteria to initiate the break-down of the polymer and to use the generated cleavage products as a carbon source. Three main types of rubber oxygenases have been described so far. One is rubber oxygenase RoxA that was first isolated from Xanthomonas sp. 35Y but was later also identified in other Gram-negative rubber-degrading species. The second type of rubber oxygenase is the latex clearing protein (Lcp) that has been regularly found in Gram-positive rubber degraders. Recently, a third type of rubber oxygenase (RoxB) with distant relationship to RoxAs was identified in Gram-negative bacteria. All rubber oxygenases described so far are haem-containing enzymes and oxidatively cleave polyisoprene to low molecular weight oligoisoprenoids with terminal CHO and CO-CH functions between a variable number of intact isoprene units, depending on the type of rubber oxygenase. This contribution summarises the properties of RoxAs, RoxBs and Lcps.
Topics: Bacteria; Bacterial Proteins; Biotechnology; Electron Spin Resonance Spectroscopy; Heme; Hemiterpenes; Latex; Oxygenases; Phylogeny; Rubber; Spectrophotometry, Ultraviolet; Xanthomonas
PubMed: 30377752
DOI: 10.1007/s00253-018-9453-z -
Biochimica Et Biophysica Acta.... Nov 2020Mammals and higher vertebrates including humans have only three members of the carotenoid cleavage dioxygenase family of enzymes. This review focuses on the two that... (Review)
Review
Mammals and higher vertebrates including humans have only three members of the carotenoid cleavage dioxygenase family of enzymes. This review focuses on the two that function as carotenoid oxygenases. β-Carotene 15,15'-dioxygenase (BCO1) catalyzes the oxidative cleavage of the central 15,15' carbon-carbon double of β-carotene bond by addition of molecular oxygen. The product of the reaction is retinaldehyde (retinal or β-apo-15-carotenal). Thus, BCO1 is the enzyme responsible for the conversion of provitamin A carotenoids to vitamin A. It also cleaves the 15,15' bond of β-apocarotenals to yield retinal and of lycopene to yield apo-15-lycopenal. β-Carotene 9',10'-dioxygenase (BCO2) catalyzes the cleavage of the 9,10 and 9',10' double bonds of a wider variety of carotenoids, including both provitamin A and non-provitamin A carotenoids, as well as the xanthophylls, lutein and zeaxanthin. Indeed, the enzyme shows a marked preference for utilization of these xanthophylls and other substrates with hydroxylated terminal rings. Studies of the phenotypes of BCO1 null, BCO2 null, and BCO1/2 double knockout mice and of humans with polymorphisms in the enzymes, has clarified the role of these enzymes in whole body carotenoid and vitamin A homeostasis. These studies also demonstrate the relationship between enzyme expression and whole body lipid and energy metabolism and oxidative stress. In addition, relationships between BCO1 and BCO2 and the development or risk of metabolic diseases, eye diseases and cancer have been observed. While the precise roles of the enzymes in the pathophysiology of most of these diseases is not presently clear, these gaps in knowledge provide fertile ground for rigorous future investigations. This article is part of a Special Issue entitled Carotenoids: Recent Advances in Cell and Molecular Biology edited by Johannes von Lintig and Loredana Quadro.
Topics: Animals; Carotenoids; Catalysis; Dioxygenases; Humans; Mice; Mice, Knockout; Oxidative Stress; Oxygenases; Vertebrates; beta-Carotene 15,15'-Monooxygenase
PubMed: 32035229
DOI: 10.1016/j.bbalip.2020.158653 -
Biochimica Et Biophysica Acta.... Nov 2020The carotenoids are terpenoid fat-soluble pigments produced by plants, algae, and several bacteria and fungi. They are ubiquitous components of animal diets. Carotenoid... (Review)
Review
The carotenoids are terpenoid fat-soluble pigments produced by plants, algae, and several bacteria and fungi. They are ubiquitous components of animal diets. Carotenoid cleavage oxygenase (CCO) superfamily members are involved in carotenoid metabolism and are present in all kingdoms of life. Throughout the animal kingdom, carotenoid oxygenases are widely distributed and they are completely absent only in two unicellular organisms, Monosiga and Leishmania. Mammals have three paralogs 15,15'-β-carotene oxygenase (BCO1), 9',10'-β-carotene oxygenase (BCO2) and RPE65. The first two enzymes are classical carotenoid oxygenases: they cleave carbon‑carbon double bonds and incorporate two atoms of oxygen in the substrate at the site of cleavage. The third, RPE65, is an unusual family member, it is the retinoid isomerohydrolase in the visual cycle that converts all-trans-retinyl ester into 11-cis-retinol. Here we discuss evolutionary aspects of the carotenoid cleavage oxygenase superfamily and their enzymology to deduce what insight we can obtain from their evolutionary conservation.
Topics: Animals; Carotenoids; Dioxygenases; Evolution, Molecular; Lipid Metabolism; Mammals; Oxygenases; beta-Carotene 15,15'-Monooxygenase; cis-trans-Isomerases
PubMed: 32061750
DOI: 10.1016/j.bbalip.2020.158665 -
Biochemical Society Transactions Oct 2020Fe(II)/2-oxoglutarate (2OG)-dependent oxygenases are a conserved enzyme class that catalyse diverse oxidative reactions across nature. In humans, these enzymes... (Review)
Review
Fe(II)/2-oxoglutarate (2OG)-dependent oxygenases are a conserved enzyme class that catalyse diverse oxidative reactions across nature. In humans, these enzymes hydroxylate a broad range of biological substrates including DNA, RNA, proteins and some metabolic intermediates. Correspondingly, members of the 2OG-dependent oxygenase superfamily have been linked to fundamental biological processes, and found dysregulated in numerous human diseases. Such findings have stimulated efforts to understand both the biochemical activities and cellular functions of these enzymes, as many have been poorly studied. In this review, we focus on human 2OG-dependent oxygenases catalysing the hydroxylation of protein and polynucleotide substrates. We discuss their modulation by changes in the cellular microenvironment, particularly with respect to oxygen, iron, 2OG and the effects of oncometabolites. We also describe emerging evidence that these enzymes are responsive to cellular stresses including hypoxia and DNA damage. Moreover, we examine how dysregulation of 2OG-dependent oxygenases is associated with human disease, and the apparent paradoxical role for some of these enzymes during cancer development. Finally, we discuss some of the challenges associated with assigning biochemical activities and cellular functions to 2OG-dependent oxygenases.
Topics: Ascorbic Acid; Biological Phenomena; Catalysis; DNA; DNA Damage; Gene Expression Regulation; Humans; Hydroxylation; Hypoxia; Ketoglutaric Acids; Mixed Function Oxygenases; Models, Molecular; Neoplasms; Oxidation-Reduction; Oxygen; Oxygenases; Protein Processing, Post-Translational; RNA
PubMed: 32985654
DOI: 10.1042/BST20190333 -
Archives of Biochemistry and Biophysics Nov 2013Carotenoids and their metabolic derivatives serve critical functions in both prokaryotic and eukaryotic cells, including pigmentation, photoprotection and photosynthesis... (Review)
Review
Carotenoids and their metabolic derivatives serve critical functions in both prokaryotic and eukaryotic cells, including pigmentation, photoprotection and photosynthesis as well as cell signaling. These organic compounds are also important for visual function in vertebrate and non-vertebrate organisms. Enzymatic transformations of carotenoids to various apocarotenoid products are catalyzed by a family of evolutionarily conserved, non-heme iron-containing enzymes named carotenoid cleavage oxygenases (CCOs). Studies have revealed that CCOs are critically involved in carotenoid homeostasis and essential for the health of organisms including humans. These enzymes typically display a high degree of regio- and stereo-selectivity, acting on specific positions of the polyene backbone located in their substrates. By oxidatively cleaving and/or isomerizing specific double bonds, CCOs generate a variety of apocarotenoid isomer products. Recent structural studies have helped illuminate the mechanisms by which CCOs mobilize their lipophilic substrates from biological membranes to perform their characteristic double bond cleavage and/or isomerization reactions. In this review, we aim to integrate structural and biochemical information about CCOs to provide insights into their catalytic mechanisms.
Topics: Animals; Bacteria; Bacterial Physiological Phenomena; Carotenoids; Catalysis; Humans; Mammals; Oxygenases; Stereoisomerism; Substrate Specificity
PubMed: 23827316
DOI: 10.1016/j.abb.2013.06.012 -
Current Opinion in Structural Biology Dec 2016The Jumonji-C (JmjC) subfamily of 2-oxoglutarate (2OG)-dependent oxygenases are of biomedical interest because of their roles in the regulation of gene expression and... (Review)
Review
The Jumonji-C (JmjC) subfamily of 2-oxoglutarate (2OG)-dependent oxygenases are of biomedical interest because of their roles in the regulation of gene expression and protein biosynthesis. Human JmjC 2OG oxygenases catalyze oxidative modifications to give either chemically stable alcohol products, or in the case of N-methyl lysine demethylation, relatively unstable hemiaminals that fragment to give formaldehyde and the demethylated product. Recent work has yielded conflicting reports as to whether some JmjC oxygenases catalyze N-methyl group demethylation or hydroxylation reactions. We review JmjC oxygenase-catalyzed reactions within the context of structural knowledge, highlighting key differences between hydroxylases and demethylases, which have the potential to inform on the possible type(s) of reactions catalyzed by partially characterized or un-characterized JmjC oxygenases in humans and other organisms.
Topics: Animals; Biocatalysis; Humans; Jumonji Domain-Containing Histone Demethylases; Mixed Function Oxygenases; Protein Multimerization; Structure-Activity Relationship
PubMed: 27309310
DOI: 10.1016/j.sbi.2016.05.013 -
Current Opinion in Chemical Biology Apr 2024The hypoxia-inducible factors are α,β-heterodimeric transcription factors that mediate the chronic response to hypoxia in humans and other animals. Protein... (Review)
Review
The hypoxia-inducible factors are α,β-heterodimeric transcription factors that mediate the chronic response to hypoxia in humans and other animals. Protein hydroxylases belonging to two different structural subfamilies of the Fe(II) and 2-oxoglutarate (2OG)-dependent oxygenase superfamily modify HIFα. HIFα prolyl-hydroxylation, as catalysed by the PHDs, regulates HIFα levels and, consequently, α,β-HIF levels. HIFα asparaginyl-hydroxylation, as catalysed by factor inhibiting HIF (FIH), regulates the transcriptional activity of α,β-HIF. The activities of the PHDs and FIH are regulated by O availability, enabling them to act as hypoxia sensors. We provide an overview of the biochemistry of the HIF hydroxylases, discussing evidence that their kinetic and structural properties may be tuned to their roles in the HIF system. Avenues for future research and therapeutic modulation are discussed.
Topics: Animals; Humans; Mixed Function Oxygenases; Transcription Factors; Hypoxia; Hydroxylation
PubMed: 38330792
DOI: 10.1016/j.cbpa.2024.102428 -
International Journal of Molecular... Jan 2022Enzymatic oxidations of thiophenes, including thiophene-containing drugs, are important for biodesulfurization of crude oil and drug metabolism of mono- and poly-cyclic... (Review)
Review
Enzymatic oxidations of thiophenes, including thiophene-containing drugs, are important for biodesulfurization of crude oil and drug metabolism of mono- and poly-cyclic thiophenes. Thiophene oxidative dearomatization pathways involve reactive metabolites, whose detection is important in the pharmaceutical industry, and are catalyzed by monooxygenase (sulfoxidation, epoxidation) and dioxygenase (sulfoxidation, dihydroxylation) enzymes. Sulfoxide and epoxide metabolites of thiophene substrates are often unstable, and, while -dihydrodiol metabolites are more stable, significant challenges are presented by both types of metabolite. Prediction of the structure, relative and absolute configuration, and enantiopurity of chiral metabolites obtained from thiophene enzymatic oxidation depends on the substrate, type of oxygenase selected, and molecular docking results. The racemization and dimerization of sulfoxides, / epimerization of dihydrodiol metabolites, and aromatization of epoxides are all factors associated with the mono- and di-oxygenase-catalyzed metabolism of thiophenes and thiophene-containing drugs and their applications in chemoenzymatic synthesis and medicine.
Topics: Biotransformation; Catalysis; Cytochrome P-450 Enzyme System; Dioxygenases; Inactivation, Metabolic; Metabolic Networks and Pathways; Mixed Function Oxygenases; Models, Molecular; Molecular Conformation; Molecular Structure; Oxidation-Reduction; Oxidative Stress; Protein Binding; Structure-Activity Relationship; Sulfoxides; Thiophenes
PubMed: 35055091
DOI: 10.3390/ijms23020909 -
International Journal of Molecular... Oct 2016Apocarotenoids are carotenoid-derived compounds widespread in all major taxonomic groups, where they play important roles in different physiological processes. In... (Review)
Review
Apocarotenoids are carotenoid-derived compounds widespread in all major taxonomic groups, where they play important roles in different physiological processes. In addition, apocarotenoids include compounds with high economic value in food and cosmetics industries. Apocarotenoid biosynthesis starts with the action of carotenoid cleavage dioxygenases (CCDs), a family of non-heme iron enzymes that catalyze the oxidative cleavage of carbon-carbon double bonds in carotenoid backbones through a similar molecular mechanism, generating aldehyde or ketone groups in the cleaving ends. From the identification of the first CCD enzyme in plants, an increasing number of CCDs have been identified in many other species, including microorganisms, proving to be a ubiquitously distributed and evolutionarily conserved enzymatic family. This review focuses on CCDs from plants, algae, fungi, and bacteria, describing recent progress in their functions and regulatory mechanisms in relation to the different roles played by the apocarotenoids in these organisms.
Topics: Bacteria; Carotenoids; Fungi; Models, Molecular; Oxygenases; Photosynthesis; Plants; Substrate Specificity
PubMed: 27792173
DOI: 10.3390/ijms17111781 -
Biochemistry Jun 2022Proteins of the HD-domain superfamily employ a conserved histidine-aspartate (HD) dyad to coordinate diverse metallocofactors. While most known HD-domain proteins are...
Proteins of the HD-domain superfamily employ a conserved histidine-aspartate (HD) dyad to coordinate diverse metallocofactors. While most known HD-domain proteins are phosphohydrolases, new additions to this superfamily have emerged such as oxygenases and lyases, expanding their functional repertoire. To date, three HD-domain oxygenases have been identified, all of which employ a mixed-valent FeFe cofactor to activate their substrates and utilize molecular oxygen to afford cleavage of C-C or C-P bonds via a diferric superoxo intermediate. Phylogenetic analysis reveals an uncharacterized multidomain protein in the pathogenic soil fungus , herein designated PhoF. PhoF consists of an N-terminal Fe/α-ketoglutarate-dependent domain resembling that of PhnY and a C-terminal HD-domain like that of PhnZ. PhnY and PhnZ are part of an organophosphonate degradation pathway in which PhnY hydroxylates 2-aminoethylphosphonic acid, and PhnZ cleaves the C-P bond of the hydroxylated product yielding phosphate and glycine. Employing electron paramagnetic resonance and Mössbauer spectroscopies in tandem with activity assays, we determined that PhoF carries out the O-dependent degradation of two aminophosphonates, demonstrating an expanded catalytic efficiency with respect to the individual, but mechanistically coupled PhnY and PhnZ. Our results recognize PhoF as a new example of an HD-domain oxygenase and show that domain fusion of an organophosphonate degradation pathway may be a strategy for disease-causing fungi to acquire increased functional versatility, potentially important for their survival.
Topics: Ferric Compounds; Fungi; Organophosphonates; Oxygen; Oxygenases; Phylogeny
PubMed: 35506879
DOI: 10.1021/acs.biochem.2c00163