The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Robert S. Haltiwanger - One of the best experts on this subject based on the ideXlab platform.
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biological functions of Fucose in mammals
Glycobiology, 2017Co-Authors: M Schneider, Robert S. Haltiwanger, Esam AlshareffiAbstract:Fucose is a 6-deoxy hexose in the l-configuration found in a large variety of different organisms. In mammals, Fucose is incorporated into N-glycans, O-glycans and glycolipids by 13 fucosyltransferases, all of which utilize the nucleotide-charged form, GDP-Fucose, to modify targets. Three of the fucosyltransferases, FUT8, FUT12/POFUT1 and FUT13/POFUT2, are essential for proper development in mice. Fucose modifications have also been implicated in many other biological functions including immunity and cancer. Congenital mutations of a Golgi apparatus localized GDP-Fucose transporter causes leukocyte adhesion deficiency type II, which results in severe developmental and immune deficiencies, highlighting the important role Fucose plays in these processes. Additionally, changes in levels of fucosylated proteins have proven as useful tools for determining cancer diagnosis and prognosis. Chemically modified Fucose analogs can be used to alter many of these Fucose dependent processes or as tools to better understand them. In this review, we summarize the known roles of Fucose in mammalian physiology and pathophysiology. Additionally, we discuss recent therapeutic advances for cancer and other diseases that are a direct result of our improved understanding of the role that Fucose plays in these systems.
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the threonine that carries Fucose but not Fucose is required for cripto to facilitate nodal signaling
Journal of Biological Chemistry, 2007Co-Authors: Changhui Ge, Robert S. Haltiwanger, Pamela StanleyAbstract:Abstract Cripto is a membrane-bound co-receptor for Nodal, a member of the transforming growth factor-β superfamily. Mouse embryos lacking either Cripto or Nodal have the same lethal phenotype at embryonic day 7.5. Previous studies suggest that O-fucosylation of the epidermal growth factor-like (EGF) repeat in Cripto is essential for the facilitation of Nodal signaling. Substitution of Ala for the Thr to which O-Fucose is attached led to functional inactivation of both human and mouse Cripto. However, embryos null for protein O-fucosyltransferase 1, the enzyme that adds O-Fucose to EGF repeats, do not exhibit a Cripto null phenotype and die at about embryonic day 9.5. This suggested that the loss of O-Fucose from the EGF repeat may not have led to the inactivation of Cripto in previous studies. Here we investigate this hypothesis and show the following: 1) protein O-fucosyltransferase 1 is indeed the enzyme that adds O-Fucose to Cripto; 2) Pofut1–/– embryonic stem cells behave the same as Pofut1+/+ embryonic stem cells in a Nodal signaling assay; 3) Pofut1–/– and Pofut1+/+ embryoid bodies are indistinguishable in their ability to differentiate into cardiomyocytes; and 4) none of 10 amino acid substitutions at Thr72, including Ser which acquires O-Fucose, rescues the activity of mouse Cripto in Nodal signaling assays. Therefore, the Thr to which O-Fucose is linked in Cripto plays a key functional role, but O-Fucose at Thr72 is not required for Cripto to function in cell-based signaling assays or in vivo. By contrast, we show that O-Fucose, and not the Thr to which it is attached, is required in the ligand-binding domain of Notch1 for Notch1 signaling.
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o fucosylation is required for adamts13 secretion
Journal of Biological Chemistry, 2007Co-Authors: Lindsay M Ricketts, Robert S. Haltiwanger, Malgosia Dlugosz, Kelvin B Luther, Elaine M MajerusAbstract:Abstract ADAMTS13 is a plasma metalloproteinase that cleaves von Willebrand factor to smaller, less thrombogenic forms. Deficiency of ADAMTS13 activity in plasma leads to thrombotic thrombocytopenic purpura. ADAMTS13 contains eight thrombospondin type 1 repeats (TSR), seven of which contain a consensus sequence for the direct addition of Fucose to the hydroxyl group of serine or threonine. Mass spectral analysis of tryptic peptides derived from human ADAMTS13 indicate that at least six of the TSRs are modified with an O-Fucose disaccharide. Analysis of [3H]Fucose metabolically incorporated into ADAMTS13 demonstrated that the disaccharide has the structure glucose-β1,3-Fucose. Mutation of the modified serine to alanine in TSR2, TSR5, TSR7, and TSR8 reduced the secretion of ADAMTS13. Mutation of more than one site dramatically reduced secretion regardless of the sites mutated. When the expression of protein O-fucosyltransferase 2 (POFUT2), the enzyme that transfers Fucose to serines in TSRs, was reduced using siRNA, the secretion of ADAMTS13 decreased. A similar outcome was observed when ADAMTS13 was expressed in a cell line unable to synthesize the donor for Fucose addition, GDP-Fucose. Although overexpression of POFUT2 did not affect the secretion of wild-type ADAMTS13, it did increase the secretion of the ADAMTS13 TSR1,2 double mutant but not that of ADAMTS13 TSR1–8 mutant. Together these findings indicate that O-fucosylation is functionally significant for secretion of ADAMTS13.
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two distinct pathways for o fucosylation of epidermal growth factor like or thrombospondin type 1 repeats
Journal of Biological Chemistry, 2006Co-Authors: Yi Luo, Aleksandra Nitalazar, Robert S. HaltiwangerAbstract:Epidermal growth factor-like (EGF) repeats and thrombospondin type 1 repeats (TSRs) are both small cysteine-knot motifs known to be O-fucosylated. The enzyme responsible for the addition of O-Fucose to EGF repeats, protein O-fucosyltransferase 1 (POFUT1), has been identified and shown to be essential in Notch signaling. Fringe, an O-Fucose β1,3-N-acetylglucosaminyltransferase, elongates O-Fucose on specific EGF repeats from Notch to form a disaccharide that can be further elongated to a tetrasaccharide. TSRs are found in many extracellular matrix proteins and are involved in protein-protein interactions. The O-Fucose moiety on TSRs can be further elongated with glucose to form a disaccharide. The discovery of O-Fucose on TSRs raised the question of whether POFUT1, or a different enzyme, adds O-Fucose to TSRs. Here we demonstrate the existence of a TSR-specific O-fucosyltransferase distinct from POFUT1. Similar to POFUT1, the novel TSR-specific O-fucosyltransferase is a soluble enzyme that requires a properly folded TSR as an acceptor substrate. In addition, we found that a previously identified Fucose-specific β1,3-glucosyltransferase adds glucose to O-Fucose on TSRs, but it does not modify O-Fucose on an EGF repeat. Similarly, Lunatic fringe, Manic fringe, and Radical fringe are all capable of modifying O-Fucose on an EGF repeat, but not on a TSR. Taken together, these results suggest that two distinct O-fucosylation pathways exist in cells, one specific for EGF repeat and the other for TSRs.
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Differential terminal fucosylation of N-linked glycans versus protein O-fucosylation in leukocyte adhesion deficiency type II (CDG IIc).
The Journal of biological chemistry, 2003Co-Authors: Laura Sturla, Robert S. Haltiwanger, Floriana Fruscione, Raajit Rampal, Amos Etzioni, Michela TonettiAbstract:LAD II/CDG IIc is a rare autosomal recessive disease characterized by a decreased expression of fucosylated antigens on cell surfaces that results in leukocyte adhesion deficiency and severe neurological and developmental abnormalities. Its molecular basis has been identified as a defect in the transporter of GDP-l-Fucose into the Golgi lumen, which reduces the availability of the substrate for fucosyltransferases. During metabolic radiolabeling experiments using [3H]Fucose, LAD II fibroblasts incorporated significantly less radiolabel compared with control cells. However, fractionation and analysis of the different classes of glycans indicated that the decrease in [3H]Fucose incorporation is not generalized and is mainly confined to terminal fucosylation of N-linked oligosaccharides. In contrast, the total levels of protein O-fucosylation, including that observed in Notch protein, were unaffected. This finding demonstrates that the decrease in GDP-l-Fucose levels in the fibroblast Golgi caused by the LAD II defect does not impair bulk protein O-fucosylation, but severely affects the bulk addition of Fucose as a terminal modification of N-linked glycans. These data suggest that the severe clinical abnormalities including neurological and developmental ones observed in at least some of the LAD II patients may be related to alteration in recognition systems involving terminal Fucose modifications of N-glycans and not be due to a defective O-fucosylation of proteins such as Notch.
Kenya Shitara - One of the best experts on this subject based on the ideXlab platform.
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establishment of a gdp mannose 4 6 dehydratase gmd knockout host cell line a new strategy for generating completely non fucosylated recombinant therapeutics
Journal of Biotechnology, 2007Co-Authors: Yutaka Kanda, Harue Imainishiya, Reiko Kunikamochi, Katsuhiro Mori, Kazuko Kitajimamiyama, Miho Inoue, Akira Okazaki, Kenya Shitara, Shigeru Iida, Mitsuo SatohAbstract:Abstract Currently, removal of core Fucose from the Fc oligosaccharides of therapeutic antibodies is widely recognized as being of great importance for the effector function of antibody-dependent cellular cytotoxicity, and α-1,6-fucosyltransferase ( FUT8 ) knockout cells have been generated as an ideal host cell line for manufacturing such therapeutics. Here, we attempted to identify genes other than FUT8 that could be targeted for the manufacture of non-fucosylated therapeutics. Loss-of-function analyses using siRNAs against three key genes involved in oligosaccharide fucosylation in Chinese hamster ovary (CHO) cells revealed that there was a positive correlation between the Fc oligosaccharide fucosylation and the mRNA expression through the origin in the cases of both GDP-Fucose 4,6-dehydratase ( GMD ) and FUT8 , but not for the GDP-Fucose transporter, suggesting that there is no functional redundancy in GMD and FUT8 . GMD knockout CHO/DG44 cells were successfully established, and were confirmed to be devoid of intracellular GDP-Fucose and to produce completely non-fucosylated antibodies. GMD knockout cells recovered their fucosylation capability through the salvage pathway upon addition of l -Fucose into the culture medium, and exhibited equable morphology, growth kinetics and recombinant protein productivity, demonstrating that loss of oligosaccharide fucosylation has no impact on these cellular phenotypes. Our results demonstrate that GMD knockout is a new strategy applicable to the manufacture of non-fucosylated therapeutic antibodies, and completely O -Fucose-negative therapeutics as well.
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Fucose removal from complex type oligosaccharide enhances the antibody dependent cellular cytotoxicity of single gene encoded bispecific antibody comprising of two single chain antibodies linked to the antibody constant region
Journal of Biochemistry, 2006Co-Authors: Akito Natsume, Mitsuo Satoh, Kazuhisa Uchida, Rinpei Niwa, Masako Wakitani, Naoko Yamaneohnuki, Emi Shojihosaka, Kenya ShitaraAbstract:Bispecific antibodies (bsAbs) have the potential to extend binding selectivity, increase avidity and exert potent cytotoxicity due to the combination of dual specificities. scFv 2 -Fc type of single-gene-encoded bispecific antibody, composed of two different single-chain Fvs and an Fc, has been reported to be capable of binding to different antigens. The aim of this study was to determine the effect of Fucose removal on effector functions of scFv 2 -Fc since Fucose depletion from oligosaccharide of human IgG1 and scFv-Fc results in significant enhancement ofADCC. We generated novel single-gene-encoded bsAb with dual specificity against tumor associated glycoprotein (TAG)-72 and MUC1 mucin as Fucose-negative scFv 2 -Fc from α-1,6-fucosyltransferase knock-out CHO cells and a highly fucosylated scFv 2 -Fc comparator from parental CHO cells. Expression, assembly and the antigen-binding activity of the scFv 2 -Fc were not influenced by removal of Fucose. The Fucose negative scFv 2 -Fc bound with higher avidity to FcyRIIIa and enhanced ADCC compared to the highly fucosylated scFv 2 -Fc. These results demonstrate that ADCC-enhancement by removal of Fucose is effective in not only whole IgG1 and scFv-Fc, but also scFv 2 -Fc targeting two different antigens, and thus increases the potential of Fucose-negative scFv 2 -Fcs as novel therapeutic candidates.
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igg subclass independent improvement of antibody dependent cellular cytotoxicity by Fucose removal from asn297 linked oligosaccharides
Journal of Immunological Methods, 2005Co-Authors: Rinpei Niwa, Mitsuo Satoh, Shigeru Iida, Kazuhisa Uchida, Akito Natsume, Aya Uehara, Masako Wakitani, Kenya ShitaraAbstract:Fucose depletion from oligosaccharides of human IgG1-type antibodies results in a great enhancement of antibody-dependent cellular cytotoxicity (ADCC). The aim of this study was to clarify the effect of Fucose removal on effector functions of all human IgG subclasses. A panel of anti-CD20 chimeric antibodies having a matched set of human heavy chain subclasses with different Fucose contents in their oligosaccharides was constructed using wild-type and fucosyltransferase-knockout Chinese hamster ovary cells as host cells. As found previously for IgG1, Fucose-negative variant of IgG2, IgG3, and IgG4 exhibited enhanced ADCC and FcgammaRIIIa binding compared with their highly fucosylated counterparts. In contrast, Fucose removal did not affect complement-dependent cytotoxicity (CDC) of any IgGs. Consequently, Fucose removal from IgG2 and IgG4 resulted in a unique effector function profile; they had potent ADCC and no CDC. In conclusion Fucose depletion can provide a panel of IgGs with enhanced ADCC without an impact on other inherent properties specific for each IgG subclass, such as CDC.
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Fucose removal from complex type oligosaccharide enhances the antibody dependent cellular cytotoxicity of single gene encoded antibody comprising a single chain antibody linked the antibody constant region
Journal of Immunological Methods, 2005Co-Authors: Akito Natsume, Mitsuo Satoh, Kazuhisa Uchida, Rinpei Niwa, Masako Wakitani, Naoko Yamaneohnuki, Emi Shojihosaka, Kenya ShitaraAbstract:Abstract Fucose removal from complex-type oligosaccharide of human IgG1-type antibody results in a great enhancement of antibody-dependent cellular cytotoxicity (ADCC). The aim of this study was to clarify the effect of Fucose removal on effector functions of a single-gene-encoded antibody with an scFv used as the binding domain. We generated both a Fucose-negative anti-tumor associated glycoprotein (TAG)-72 scFv-Fc using α-1,6-fucosyltransferase knock-out CHO cells and a highly fucosylated scFv-Fc from parental CHO cells. Expression, assembly and antigen binding activity of the scFv-Fcs were not influenced by Fucose removal. The scFv-Fc lacking Fucose exhibited significantly more potent FcγRIIIa binding and ADCC compared to highly fucosylated scFv-Fc. These results prove that ADCC enhancement by Fucose-removal is effective in not only whole IgG1, but also scFv-Fc, and thus increases the potential of Fc-fusion proteins as therapeutic candidates.
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enhanced natural killer cell binding and activation by low Fucose igg1 antibody results in potent antibody dependent cellular cytotoxicity induction at lower antigen density
Clinical Cancer Research, 2005Co-Authors: Rinpei Niwa, Aya Uehara, Mikiko Sakurada, Yukari Kobayashi, Kouji Matsushima, Ryuzo Ueda, Kazuyasu Nakamura, Kenya ShitaraAbstract:Purpose: Recent studies have revealed that Fucose removal from the oligosaccharides of human IgG1 antibodies results in a significant enhancement of antibody-dependent cellular cytotoxicity (ADCC) via improved IgG1 binding to FcγRIIIa. In this report, we investigated the relationship between enhanced ADCC and antigen density on target cells using IgG1 antibodies with reduced Fucose. Experimental Design: Using EL4 cell-derived transfectants with differential expression levels of exogenous human CC chemokine receptor 4 or human CD20 as target cells, ADCC of Fucose variants of chimeric IgG1 antibodies specific for these antigens were measured. We further investigated IgG1 binding to natural killer (NK) cells and NK cell activation during ADCC induction to elucidate the mechanism by which low-Fucose IgG1 induces ADCC upon target cells with low antigen expression. Results: Low-Fucose IgG1s showed potent ADCC at low antigen densities at which their corresponding high-Fucose counterparts could not induce measurable ADCC. The quantitative analysis revealed that Fucose depletion could reduce the antigen amount on target cells required for constant degrees of ADCC induction by 10-fold for CC chemokine receptor 4 and 3-fold for CD20. IgG1 binding to NK cells was increased by ligating IgG1 with clustered antigen, especially for low-Fucose IgG1. Up-regulation of an activation marker, CD69, on NK cells, particularly the CD56 dim subset, in the presence of both the antibody and target cells was much greater for the low-Fucose antibodies. Conclusions: Our data showed that Fucose removal from IgG1 could reduce the antigen amount required for ADCC induction via efficient recruitment and activation of NK cells.
Michela Tonetti - One of the best experts on this subject based on the ideXlab platform.
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core fucosylation of n linked glycans in leukocyte adhesion deficiency congenital disorder of glycosylation iic fibroblasts
Glycobiology, 2005Co-Authors: Laura Sturla, Floriana Fruscione, Katsuhisa Noda, Eiji Miyoshi, Naoyuki Taniguchi, Paola Contini, Michela TonettiAbstract:Leukocyte adhesion deficiency/congenital disorder of glycosylation IIc (LAD II/CDG IIc) is a genetic disease characterized by a decreased expression of Fucose in glycoconjugates, resulting in leukocyte adhesion deficiency and severe morphological and neurological abnormalities. The biochemical defect is a reduced transport of guanosine diphosphate-L-Fucose (GDP-L-Fucose) from cytosol into the Golgi compartment, which reduces its availability as substrate for fucosyltransferases. The aim of this study was to determine the effects of a limited supply of GDP-L-Fucose inside the Golgi on core fucosylation (alpha1,6-Fucose linked to core N-acetylglucosamine [GlcNAc]) of N-linked glycans in LAD II fibroblasts. The results showed that, although [3H]Fucose incorporation was generally reduced in LAD II cells, core fucosylation was affected to a greater extent compared with other types of fucosylation of N-linked oligosaccharides. In particular, core fucosylation was found to be nearly absent in biantennary negatively charged oligosaccharides, whereas other types of structures, in particular triantennary neutral species, were less affected by the reduction. Expression and activity of alpha1,6-fucosyltransferase (FUT8) in control and LAD II fibroblasts were comparable, thus excluding the possibility of a decreased activity of the transferase. The data obtained confirm that the concentration of GDP-L-Fucose inside the Golgi can differentially affect the various types of fucosylation in vivo and also indicate that core fucosylation is not dependent only on the availability of GDP-L-Fucose, but it is significantly influenced by the type of oligosaccharide structure. The relevant reduction in core fucosylation observed in some species of oligosaccharides could also provide clues for the identification of glycans involved in the severe developmental abnormalities observed in LAD II.
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Differential terminal fucosylation of N-linked glycans versus protein O-fucosylation in leukocyte adhesion deficiency type II (CDG IIc).
The Journal of biological chemistry, 2003Co-Authors: Laura Sturla, Robert S. Haltiwanger, Floriana Fruscione, Raajit Rampal, Amos Etzioni, Michela TonettiAbstract:LAD II/CDG IIc is a rare autosomal recessive disease characterized by a decreased expression of fucosylated antigens on cell surfaces that results in leukocyte adhesion deficiency and severe neurological and developmental abnormalities. Its molecular basis has been identified as a defect in the transporter of GDP-l-Fucose into the Golgi lumen, which reduces the availability of the substrate for fucosyltransferases. During metabolic radiolabeling experiments using [3H]Fucose, LAD II fibroblasts incorporated significantly less radiolabel compared with control cells. However, fractionation and analysis of the different classes of glycans indicated that the decrease in [3H]Fucose incorporation is not generalized and is mainly confined to terminal fucosylation of N-linked oligosaccharides. In contrast, the total levels of protein O-fucosylation, including that observed in Notch protein, were unaffected. This finding demonstrates that the decrease in GDP-l-Fucose levels in the fibroblast Golgi caused by the LAD II defect does not impair bulk protein O-fucosylation, but severely affects the bulk addition of Fucose as a terminal modification of N-linked glycans. These data suggest that the severe clinical abnormalities including neurological and developmental ones observed in at least some of the LAD II patients may be related to alteration in recognition systems involving terminal Fucose modifications of N-glycans and not be due to a defective O-fucosylation of proteins such as Notch.
Paulo As Mourao - One of the best experts on this subject based on the ideXlab platform.
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unveiling the structure of sulfated Fucose rich polysaccharides via nuclear magnetic resonance spectroscopy
Current Opinion in Structural Biology, 2018Co-Authors: Paulo As Mourao, Eduardo Vilanova, Paulo A G SoaresAbstract:Sulfated fucans from marine invertebrates are composed of regular repetitive Fucose building-blocks with sulfation patterns differing in a species-specific manner. These polysaccharides can act as mediators of the acrosome reaction of sea-urchins or play a structural role in the body-wall of sea-cucumbers. Other Fucose-rich polysaccharides found in the body-wall of sea-cucumbers are the fucosylated chondroitin sulfates composed of a vertebrate-like chondroitin sulfate decorated with species-specific Fucose branches. Fine-tuning structural determinations of these polysaccharides have been accomplished since the 1980s almost exclusively via high-resolution NMR. In this review, we present an overview on NMR-based structural and conformational analyses of these sulfated Fucose-rich polysaccharides. This constitutes an outstanding example of the potential of NMR in studying the chemical aspects of complex carbohydrates.
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distinct structures of the α Fucose branches in fucosylated chondroitin sulfates do not affect their anticoagulant activity
Glycobiology, 2015Co-Authors: Gustavo R C Santos, Eduardo Vilanova, Bianca F Glauser, Luane A Parreiras, Paulo As MouraoAbstract:Fucosylated chondroitin sulfate (FCS) is a glycosaminoglycan found in sea cucumbers. It has a backbone like that of mammalian chondroitin sulfate (4-β-d-GlcA-1→3-β-d-GalNAc-1)n but substituted at the 3rd position of the β-d-glururonic acid residues with α-Fucose branches. The structure of these branches varies among FCSs extracted from different species of sea cucumbers, as revealed by solution NMR spectroscopy. Some species (Isostichopus badionotus and Patalus mollis) contain branches formed by single α-Fucose residues but with variable sulfation patterns (2,4-, 3,4- and 4-sulfation). FCS from Ludwigothurea grisea is distinguished because it contains preponderant branches formed by disaccharide units containing non-sulfated and 3-sulfated α-Fucose units at the reducing and non-reducing ends, respectively. Despite the structural variability on their α-Fucose branches, these FCSs have similar anticoagulant action on assays using purified reagents. They have serpin-dependent and serpin-independent effects. Pharmacological assays using experimental animals showed that the three types of FCSs have similar antithrombotic effect and bleeding tendency. They also activate factor XII on the same range of concentration. Based on these observations, we proposed that only few sulfated α-Fucose branches along the FCS chain are enough to assure the binding of this glycosaminoglycan to proteins of the coagulation system. Substitution with additional sulfated α-Fucose does not increase further the activity. Overall, the use of FCSs with marked variability on their branches of α-Fucose allowed us to establish correlations between structures vs biological effects of these glycosaminoglycans on a more refined basis. It opens new avenues for therapeutic intervention using FCSs.
Stefan P Albaum - One of the best experts on this subject based on the ideXlab platform.
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a systems biology approach reveals major metabolic changes in the thermoacidophilic archaeon sulfolobus solfataricus in response to the carbon source l Fucose versus d glucose
Molecular Microbiology, 2016Co-Authors: Jacqueline Wolf, Benjamin H Meyer, Lu Shen, Andreas Albersmeier, Helge Stark, Katharina Fafenrot, Trong Khoa Pham, Katrin Muller, Lena Hoffmann, Stefan P AlbaumAbstract:Archaea are characterised by a complex metabolism with many unique enzymes that differ from their bacterial and eukaryotic counterparts. The thermoacidophilic archaeon Sulfolobus solfataricus is known for its metabolic versatility and is able to utilize a great variety of different carbon sources. However, the underlying degradation pathways and their regulation are often unknown. In this work, the growth on different carbon sources was analysed, using an integrated systems biology approach. The comparison of growth on L-Fucose and D-glucose allows first insights into the genome-wide changes in response to the two carbon sources and revealed a new pathway for L-Fucose degradation in S. solfataricus. During growth on L-Fucose major changes in the central carbon metabolic network, as well as an increased activity of the glyoxylate bypass and the 3-hydroxypropionate/4-hydroxybutyrate cycle were observed. Within the newly discovered pathway for L-Fucose degradation the following key reactions were identified: (i) L-Fucose oxidation to L-fuconate via a dehydrogenase, (ii) dehydration to 2-keto-3-deoxy-L-fuconate via dehydratase, (iii) 2-keto-3-deoxy-L-fuconate cleavage to pyruvate and L-lactaldehyde via aldolase and (iv) L-lactaldehyde conversion to L-lactate via aldehyde dehydrogenase. This pathway as well as L-Fucose transport shows interesting overlaps to the D-arabinose pathway, representing another example for pathway promiscuity in Sulfolobus species.
