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Jay D Keasling - One of the best experts on this subject based on the ideXlab platform.
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combinatorial expression of bacterial whole Mevalonate pathway for the production of β carotene in e coli
Journal of Biotechnology, 2009Co-Authors: Sanghwal Yoon, Deokkun Oh, Heejeong Jang, Jay D KeaslingAbstract:Abstract The increased synthesis of building blocks of IPP (isopentenyl diphosphate) and DMAPP (dimethylallyl diphosphate) through metabolic engineering is a way to enhance the production of carotenoids. Using E. coli as a host, IPP and DMAPP supply can be increased significantly through the introduction of foreign MVA (Mevalonate) pathway into it. The MVA pathway is split into two parts with the top and bottom portions supplying Mevalonate from acetyl-CoA, and IPP and DMAPP from Mevalonate, respectively. The bottom portions of MVA pathway from Streptococcus pneumonia, Enterococcus faecalis, Staphylococcus aureus, Streptococcus pyogenes and Saccharomyces cerevisiae were compared with exogenous Mevalonate supplementation for β-carotene production in recombinant Escherichia coli harboring β-carotene synthesis genes. The E. coli harboring the bottom MVA pathway of S. pneumoniae produced the highest amount of β-carotene. The top portions of MVA pathway were also compared and the top MVA pathway of E. faecalis was found out to be the most efficient for Mevalonate production in E. coli. The whole MVA pathway was constructed by combining the bottom and top portions of MVA pathway of S. pneumoniae and E. faecalis, respectively. The recombinant E. coli harboring the whole MVA pathway and β-carotene synthesis genes produced high amount of β-carotene even without exogenous Mevalonate supplementation. When comparing various E. coli strains – MG1655, DH5α, S17-1, XL1-Blue and BL21 – the DH5α was found to be the best β-carotene producer. Using glycerol as the carbon source for β-carotene production was found to be superior to glucose, galactose, xylose and maltose. The recombinant E. coli DH5α harboring the whole MVA pathway and β-carotene synthesis genes produced β-carotene of 465 mg/L at glycerol concentration of 2% (w/v).
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combinatorial expression of bacterial whole Mevalonate pathway for the production of β carotene in e coli
Journal of Biotechnology, 2009Co-Authors: Sanghwal Yoon, Jay D Keasling, Sookhee Lee, Jaeyean Kim, Amitabha Das, Heekyoung Ryu, Heejeong Jang, Seonwon KimAbstract:The increased synthesis of building blocks of IPP (isopentenyl diphosphate) and DMAPP (dimethylallyl diphosphate) through metabolic engineering is a way to enhance the production of carotenoids. Using E. coli as a host, IPP and DMAPP supply can be increased significantly through the introduction of foreign MVA (Mevalonate) pathway into it. The MVA pathway is split into two parts with the top and bottom portions supplying Mevalonate from acetyl-CoA, and IPP and DMAPP from Mevalonate, respectively. The bottom portions of MVA pathway from Streptococcus pneumonia, Enterococcus faecalis, Staphylococcus aureus, Streptococcus pyogenes and Saccharomyces cerevisiae were compared with exogenous Mevalonate supplementation for beta-carotene production in recombinant Escherichia coli harboring beta-carotene synthesis genes. The E. coli harboring the bottom MVA pathway of S. pneumoniae produced the highest amount of beta-carotene. The top portions of MVA pathway were also compared and the top MVA pathway of E. faecalis was found out to be the most efficient for Mevalonate production in E. coli. The whole MVA pathway was constructed by combining the bottom and top portions of MVA pathway of S. pneumoniae and E. faecalis, respectively. The recombinant E. coli harboring the whole MVA pathway and beta-carotene synthesis genes produced high amount of beta-carotene even without exogenous Mevalonate supplementation. When comparing various E. coli strains - MG1655, DH5alpha, S17-1, XL1-Blue and BL21 - the DH5alpha was found to be the best beta-carotene producer. Using glycerol as the carbon source for beta-carotene production was found to be superior to glucose, galactose, xylose and maltose. The recombinant E. coli DH5alpha harboring the whole MVA pathway and beta-carotene synthesis genes produced beta-carotene of 465mg/L at glycerol concentration of 2% (w/v).
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increased β carotene production in recombinant escherichia coli harboring an engineered isoprenoid precursor pathway with Mevalonate addition
Biotechnology Progress, 2008Co-Authors: Sanghwal Yoon, Hyemin Park, Myungsuk Choi, Deokkun Oh, Jay D KeaslingAbstract:When pT-LYCm4 containing lycopene synthetic genes was co-transformed with pSUcrtY or pSHcrtY containing crtY gene of Pantoea ananatis (P. ananatis )o rPantoea agglomerans(P. agglomerans), ‚-carotene productions of 36 and 35 mg/L were obtained, respectively. No lycopene was detected in the ‚-carotene production culture. pT-HB, constructed by addition of P. ananatis crtY gene into pT-LYCm4, was used for co-transformation with pSdxs and pSSN12Didi, which increased isopentenyl diphosphate and dimethylallyl diphosphate synthesis. ‚-Carotene production significantly increased 1.5-fold (51 mg/L) with the amplification of the dxs gene through pSdxs and 4-fold (135 mg/L) with the Mevalonate bottom pathway of pSSN12Didi in the presence of 3.3 mM Mevalonate. The pT-DHB, constructed by integrating the dxs gene into pT-HB, was used for cotransformation of Escherichia coli (E. coli) harboring pSSN12Didi, resulting in ‚-carotene production of 141 mg/L. Recombinant E. coli harboring pT-DHB and pSSN12Didi was used to maximize‚-carotene production by adjusting the available amounts of glycerol, a carbon source, and Mevalonate, the precursor of the Mevalonate bottom pathway. When recombinant E. coli was given 16.5 mM Mevalonate and 2.5% (w/v) glycerol, ‚-carotene production of 503 mg/L in concentration and 49.3 mg/g DCW in content was obtained at 144 h, which was the highest level of carotenoid production in E. coli ever reported in the literature.
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increased β carotene production in recombinant escherichia coli harboring an engineered isoprenoid precursor pathway with Mevalonate addition
Biotechnology Progress, 2008Co-Authors: Sanghwal Yoon, Hyemin Park, Myungsuk Choi, Jay D Keasling, Jueun Kim, Sookhee Lee, Jaeyean Kim, Seonwon KimAbstract:When pT-LYCm4 containing lycopene synthetic genes was co-transformed with pSUcrtY or pSHcrtY containing crtY gene of Pantoea ananatis (P. ananatis) or Pantoea agglomerans (P. agglomerans), beta-carotene productions of 36 and 35 mg/L were obtained, respectively. No lycopene was detected in the beta-carotene production culture. pT-HB, constructed by addition of P. ananatis crtY gene into pT-LYCm4, was used for co-transformation with pSdxs and pSSN12Didi, which increased isopentenyl diphosphate and dimethylallyl diphosphate synthesis. beta-Carotene production significantly increased 1.5-fold (51 mg/L) with the amplification of the dxs gene through pSdxs and 4-fold (135 mg/L) with the Mevalonate bottom pathway of pSSN12Didi in the presence of 3.3 mM Mevalonate. The pT-DHB, constructed by integrating the dxs gene into pT-HB, was used for cotransformation of Escherichia coli (E. coli) harboring pSSN12Didi, resulting in beta-carotene production of 141 mg/L. Recombinant E. coli harboring pT-DHB and pSSN12Didi was used to maximize beta-carotene production by adjusting the available amounts of glycerol, a carbon source, and Mevalonate, the precursor of the Mevalonate bottom pathway. When recombinant E. coli was given 16.5 mM Mevalonate and 2.5% (w/v) glycerol, beta-carotene production of 503 mg/L in concentration and 49.3 mg/g DCW in content was obtained at 144 h, which was the highest level of carotenoid production in E. coli ever reported in the literature.
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engineering of the pyruvate dehydrogenase bypass in saccharomyces cerevisiae for high level production of isoprenoids
Metabolic Engineering, 2007Co-Authors: Yoichiro Shiba, Eric M Paradise, James P Kirby, Daekyun Ro, Jay D KeaslingAbstract:Amorphadiene, a sesquiterpene precursor to the anti-malarial drug artemisinin, is synthesized by the cyclization of farnesyl pyrophosphate (FPP). Saccharomyces cerevisiae produces FPP through the Mevalonate pathway using acetyl-CoA as a starting compound. In order to enhance the supply of acetyl-CoA to the Mevalonate pathway and achieve high-level production of amorphadiene, we engineered the pyruvate dehydrogenase bypass in S. cerevisiae. Overproduction of acetaldehyde dehydrogenase and introduction of a Salmonella enterica acetyl-CoA synthetase variant increased the carbon flux into the Mevalonate pathway resulting in increased amorphadiene production. This work will be generally applicable to the production of a broad range of isoprenoids in yeast.
Sanghwal Yoon - One of the best experts on this subject based on the ideXlab platform.
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combinatorial expression of bacterial whole Mevalonate pathway for the production of β carotene in e coli
Journal of Biotechnology, 2009Co-Authors: Sanghwal Yoon, Jay D Keasling, Sookhee Lee, Jaeyean Kim, Amitabha Das, Heekyoung Ryu, Heejeong Jang, Seonwon KimAbstract:The increased synthesis of building blocks of IPP (isopentenyl diphosphate) and DMAPP (dimethylallyl diphosphate) through metabolic engineering is a way to enhance the production of carotenoids. Using E. coli as a host, IPP and DMAPP supply can be increased significantly through the introduction of foreign MVA (Mevalonate) pathway into it. The MVA pathway is split into two parts with the top and bottom portions supplying Mevalonate from acetyl-CoA, and IPP and DMAPP from Mevalonate, respectively. The bottom portions of MVA pathway from Streptococcus pneumonia, Enterococcus faecalis, Staphylococcus aureus, Streptococcus pyogenes and Saccharomyces cerevisiae were compared with exogenous Mevalonate supplementation for beta-carotene production in recombinant Escherichia coli harboring beta-carotene synthesis genes. The E. coli harboring the bottom MVA pathway of S. pneumoniae produced the highest amount of beta-carotene. The top portions of MVA pathway were also compared and the top MVA pathway of E. faecalis was found out to be the most efficient for Mevalonate production in E. coli. The whole MVA pathway was constructed by combining the bottom and top portions of MVA pathway of S. pneumoniae and E. faecalis, respectively. The recombinant E. coli harboring the whole MVA pathway and beta-carotene synthesis genes produced high amount of beta-carotene even without exogenous Mevalonate supplementation. When comparing various E. coli strains - MG1655, DH5alpha, S17-1, XL1-Blue and BL21 - the DH5alpha was found to be the best beta-carotene producer. Using glycerol as the carbon source for beta-carotene production was found to be superior to glucose, galactose, xylose and maltose. The recombinant E. coli DH5alpha harboring the whole MVA pathway and beta-carotene synthesis genes produced beta-carotene of 465mg/L at glycerol concentration of 2% (w/v).
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combinatorial expression of bacterial whole Mevalonate pathway for the production of β carotene in e coli
Journal of Biotechnology, 2009Co-Authors: Sanghwal Yoon, Deokkun Oh, Heejeong Jang, Jay D KeaslingAbstract:Abstract The increased synthesis of building blocks of IPP (isopentenyl diphosphate) and DMAPP (dimethylallyl diphosphate) through metabolic engineering is a way to enhance the production of carotenoids. Using E. coli as a host, IPP and DMAPP supply can be increased significantly through the introduction of foreign MVA (Mevalonate) pathway into it. The MVA pathway is split into two parts with the top and bottom portions supplying Mevalonate from acetyl-CoA, and IPP and DMAPP from Mevalonate, respectively. The bottom portions of MVA pathway from Streptococcus pneumonia, Enterococcus faecalis, Staphylococcus aureus, Streptococcus pyogenes and Saccharomyces cerevisiae were compared with exogenous Mevalonate supplementation for β-carotene production in recombinant Escherichia coli harboring β-carotene synthesis genes. The E. coli harboring the bottom MVA pathway of S. pneumoniae produced the highest amount of β-carotene. The top portions of MVA pathway were also compared and the top MVA pathway of E. faecalis was found out to be the most efficient for Mevalonate production in E. coli. The whole MVA pathway was constructed by combining the bottom and top portions of MVA pathway of S. pneumoniae and E. faecalis, respectively. The recombinant E. coli harboring the whole MVA pathway and β-carotene synthesis genes produced high amount of β-carotene even without exogenous Mevalonate supplementation. When comparing various E. coli strains – MG1655, DH5α, S17-1, XL1-Blue and BL21 – the DH5α was found to be the best β-carotene producer. Using glycerol as the carbon source for β-carotene production was found to be superior to glucose, galactose, xylose and maltose. The recombinant E. coli DH5α harboring the whole MVA pathway and β-carotene synthesis genes produced β-carotene of 465 mg/L at glycerol concentration of 2% (w/v).
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increased β carotene production in recombinant escherichia coli harboring an engineered isoprenoid precursor pathway with Mevalonate addition
Biotechnology Progress, 2008Co-Authors: Sanghwal Yoon, Hyemin Park, Myungsuk Choi, Deokkun Oh, Jay D KeaslingAbstract:When pT-LYCm4 containing lycopene synthetic genes was co-transformed with pSUcrtY or pSHcrtY containing crtY gene of Pantoea ananatis (P. ananatis )o rPantoea agglomerans(P. agglomerans), ‚-carotene productions of 36 and 35 mg/L were obtained, respectively. No lycopene was detected in the ‚-carotene production culture. pT-HB, constructed by addition of P. ananatis crtY gene into pT-LYCm4, was used for co-transformation with pSdxs and pSSN12Didi, which increased isopentenyl diphosphate and dimethylallyl diphosphate synthesis. ‚-Carotene production significantly increased 1.5-fold (51 mg/L) with the amplification of the dxs gene through pSdxs and 4-fold (135 mg/L) with the Mevalonate bottom pathway of pSSN12Didi in the presence of 3.3 mM Mevalonate. The pT-DHB, constructed by integrating the dxs gene into pT-HB, was used for cotransformation of Escherichia coli (E. coli) harboring pSSN12Didi, resulting in ‚-carotene production of 141 mg/L. Recombinant E. coli harboring pT-DHB and pSSN12Didi was used to maximize‚-carotene production by adjusting the available amounts of glycerol, a carbon source, and Mevalonate, the precursor of the Mevalonate bottom pathway. When recombinant E. coli was given 16.5 mM Mevalonate and 2.5% (w/v) glycerol, ‚-carotene production of 503 mg/L in concentration and 49.3 mg/g DCW in content was obtained at 144 h, which was the highest level of carotenoid production in E. coli ever reported in the literature.
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increased β carotene production in recombinant escherichia coli harboring an engineered isoprenoid precursor pathway with Mevalonate addition
Biotechnology Progress, 2008Co-Authors: Sanghwal Yoon, Hyemin Park, Myungsuk Choi, Jay D Keasling, Jueun Kim, Sookhee Lee, Jaeyean Kim, Seonwon KimAbstract:When pT-LYCm4 containing lycopene synthetic genes was co-transformed with pSUcrtY or pSHcrtY containing crtY gene of Pantoea ananatis (P. ananatis) or Pantoea agglomerans (P. agglomerans), beta-carotene productions of 36 and 35 mg/L were obtained, respectively. No lycopene was detected in the beta-carotene production culture. pT-HB, constructed by addition of P. ananatis crtY gene into pT-LYCm4, was used for co-transformation with pSdxs and pSSN12Didi, which increased isopentenyl diphosphate and dimethylallyl diphosphate synthesis. beta-Carotene production significantly increased 1.5-fold (51 mg/L) with the amplification of the dxs gene through pSdxs and 4-fold (135 mg/L) with the Mevalonate bottom pathway of pSSN12Didi in the presence of 3.3 mM Mevalonate. The pT-DHB, constructed by integrating the dxs gene into pT-HB, was used for cotransformation of Escherichia coli (E. coli) harboring pSSN12Didi, resulting in beta-carotene production of 141 mg/L. Recombinant E. coli harboring pT-DHB and pSSN12Didi was used to maximize beta-carotene production by adjusting the available amounts of glycerol, a carbon source, and Mevalonate, the precursor of the Mevalonate bottom pathway. When recombinant E. coli was given 16.5 mM Mevalonate and 2.5% (w/v) glycerol, beta-carotene production of 503 mg/L in concentration and 49.3 mg/g DCW in content was obtained at 144 h, which was the highest level of carotenoid production in E. coli ever reported in the literature.
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coenzyme q10 production in recombinant escherichia coli strains engineered with a heterologous decaprenyl diphosphate synthase gene and foreign Mevalonate pathway
Metabolic Engineering, 2006Co-Authors: Hossein Shahbani Zahiri, Sanghwal Yoon, Jay D Keasling, Sung Chul Yoon, Yong Chul ShinAbstract:Abstract In the present work, Escherichia coli DH5α was metabolically engineered for CoQ10 production by the introduction of decaprenyl diphosphate synthase gene (ddsA) from Agrobacterium tumefaciens. Grown in 2YTG medium (1.6% tryptone, 1% yeast extract, 0.5% NaCl, and 0.5% glycerol) with an initial pH of 7, the recombinant E. coli was capable of CoQ10 production up to 470 μg/gDCW (dry cell weight). This value could be further elevated to 900 μg/gDCW simply by increasing the initial culture pH from 7 to 9. Supplementation of 4-hydroxy benzoate did not improve the productivity any further. However, engineering of a lower Mevalonate semi-pathway so as to increase the isopentenyl diphosphate (IPP) supply of the recombinant strain using exogenous Mevalonate efficiently increased the CoQ10 production. Lower Mevalonate semi-pathways of Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae, Enterococcus faecalis, and Saccharomyces cerevisiae were tested. Among these, the pathway of Streptococcus pneumoniae proved to be superior, yielding CoQ10 production of 2700±115 μg/gDCW when supplemented with exogenous Mevalonate of 3 mM. In order to construct a complete Mevalonate pathway, the upper semi-pathway of the same bacterium, Streptococcus pneumoniae, was recruited. In a recombinant E. coli DH5α harboring three plasmids encoding for upper and lower Mevalonate semi-pathways as well as DdsA enzyme, the heterologous Mevalonate pathway could convert endogenous acetyl-CoA to IPP, resulting in CoQ10 production of up to 2428±75 μg/gDCW, without Mevalonate supplementation. In contrast, a whole Mevalonate pathway constructed in a single operon was found to be less efficient. However, it provided CoQ10 production of up to 1706±86 μg/gDCW, which was roughly 1.9 times higher than that obtained by ddsA alone.
Seonwon Kim - One of the best experts on this subject based on the ideXlab platform.
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combinatorial expression of bacterial whole Mevalonate pathway for the production of β carotene in e coli
Journal of Biotechnology, 2009Co-Authors: Sanghwal Yoon, Jay D Keasling, Sookhee Lee, Jaeyean Kim, Amitabha Das, Heekyoung Ryu, Heejeong Jang, Seonwon KimAbstract:The increased synthesis of building blocks of IPP (isopentenyl diphosphate) and DMAPP (dimethylallyl diphosphate) through metabolic engineering is a way to enhance the production of carotenoids. Using E. coli as a host, IPP and DMAPP supply can be increased significantly through the introduction of foreign MVA (Mevalonate) pathway into it. The MVA pathway is split into two parts with the top and bottom portions supplying Mevalonate from acetyl-CoA, and IPP and DMAPP from Mevalonate, respectively. The bottom portions of MVA pathway from Streptococcus pneumonia, Enterococcus faecalis, Staphylococcus aureus, Streptococcus pyogenes and Saccharomyces cerevisiae were compared with exogenous Mevalonate supplementation for beta-carotene production in recombinant Escherichia coli harboring beta-carotene synthesis genes. The E. coli harboring the bottom MVA pathway of S. pneumoniae produced the highest amount of beta-carotene. The top portions of MVA pathway were also compared and the top MVA pathway of E. faecalis was found out to be the most efficient for Mevalonate production in E. coli. The whole MVA pathway was constructed by combining the bottom and top portions of MVA pathway of S. pneumoniae and E. faecalis, respectively. The recombinant E. coli harboring the whole MVA pathway and beta-carotene synthesis genes produced high amount of beta-carotene even without exogenous Mevalonate supplementation. When comparing various E. coli strains - MG1655, DH5alpha, S17-1, XL1-Blue and BL21 - the DH5alpha was found to be the best beta-carotene producer. Using glycerol as the carbon source for beta-carotene production was found to be superior to glucose, galactose, xylose and maltose. The recombinant E. coli DH5alpha harboring the whole MVA pathway and beta-carotene synthesis genes produced beta-carotene of 465mg/L at glycerol concentration of 2% (w/v).
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increased β carotene production in recombinant escherichia coli harboring an engineered isoprenoid precursor pathway with Mevalonate addition
Biotechnology Progress, 2008Co-Authors: Sanghwal Yoon, Hyemin Park, Myungsuk Choi, Jay D Keasling, Jueun Kim, Sookhee Lee, Jaeyean Kim, Seonwon KimAbstract:When pT-LYCm4 containing lycopene synthetic genes was co-transformed with pSUcrtY or pSHcrtY containing crtY gene of Pantoea ananatis (P. ananatis) or Pantoea agglomerans (P. agglomerans), beta-carotene productions of 36 and 35 mg/L were obtained, respectively. No lycopene was detected in the beta-carotene production culture. pT-HB, constructed by addition of P. ananatis crtY gene into pT-LYCm4, was used for co-transformation with pSdxs and pSSN12Didi, which increased isopentenyl diphosphate and dimethylallyl diphosphate synthesis. beta-Carotene production significantly increased 1.5-fold (51 mg/L) with the amplification of the dxs gene through pSdxs and 4-fold (135 mg/L) with the Mevalonate bottom pathway of pSSN12Didi in the presence of 3.3 mM Mevalonate. The pT-DHB, constructed by integrating the dxs gene into pT-HB, was used for cotransformation of Escherichia coli (E. coli) harboring pSSN12Didi, resulting in beta-carotene production of 141 mg/L. Recombinant E. coli harboring pT-DHB and pSSN12Didi was used to maximize beta-carotene production by adjusting the available amounts of glycerol, a carbon source, and Mevalonate, the precursor of the Mevalonate bottom pathway. When recombinant E. coli was given 16.5 mM Mevalonate and 2.5% (w/v) glycerol, beta-carotene production of 503 mg/L in concentration and 49.3 mg/g DCW in content was obtained at 144 h, which was the highest level of carotenoid production in E. coli ever reported in the literature.
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enhanced lycopene production in escherichia coli engineered to synthesize isopentenyl diphosphate and dimethylallyl diphosphate from Mevalonate
Biotechnology and Bioengineering, 2006Co-Authors: Sanghwal Yoon, Jay D Keasling, Yong Chul Shin, Youngmi Lee, Jueun Kim, Sookhee Lee, Joo Hee Lee, Jaeyean Kim, Kyunghwa Jung, Seonwon KimAbstract:To increase expression of lycopene synthetic genes crtE, crtB, crtI, and ipiHP1, the four exogenous genes were cloned into a high copy pTrc99A vector with a strong trc promoter. Recombinant Escherichia coli harboring pT-LYCm4 produced 17 mg/L of lycopene. The Mevalonate lower pathway, composed of mvaK1, mvaK2, mvaD, and idi, was engineered to produce pSSN12Didi for an efficient supply of the lycopene building blocks, isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP). Mevalonate was supplied as a substrate for the Mevalonate lower pathway. Lycopene production in E. coli harboring pT-LYCm4 and pSSN12Didi with supplementation of 3.3 mM Mevalonate was more than threefold greater than bacteria with pT-LYCm4 only. Lycopene production was dependent on Mevalonate concentration supplied in the culture. Clump formation was observed as cells accumulated more lycopene. Further clumping was prevented by adding the surfactant Tween 80 0.5% (w/v), which also increased lycopene production and cell growth. When recombinant E. coli harboring pT-LYCm4 and pSSN12Didi was cultivated in 2YT medium containing 2% (w/v) glycerol as a carbon source, 6.6 mM Mevalonate for the Mevalonate lower pathway, and 0.5% (w/v) Tween 80 to prevent clump formation, lycopene production was 102 mg/L and 22 mg/g dry cell weight, and cell growth had an OD(600) value of 15 for 72 h.
Christian Schwentner - One of the best experts on this subject based on the ideXlab platform.
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1320 altered expression of farnesyl pyrophosphate synthase in prostate cancer evidence for a role of the Mevalonate pathway for disease progression
The Journal of Urology, 2012Co-Authors: Tilman Todenhöfer, Jörg Hennenlotter, Ursula Kühs, Valentina Gerber, Ulrich Vogel, Stefan Aufderklamm, Arnulf Stenzl, Christian SchwentnerAbstract:Background Preclinical studies demonstrated effects of drugs inhibiting the Mevalonate pathway including nitrogen-containing bisphosphonates (N-BPs) and statins on tumor growth and progression. The exact role of this pathway in prostate cancer (PC) has not been identified yet. Herein, we evaluate the expression of farnesyl pyrophosphate synthase (FPPS), the key enzyme of the Mevalonate pathway, in PC.
Anna Simon - One of the best experts on this subject based on the ideXlab platform.
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hyper igd syndrome Mevalonate kinase deficiency what is new
Seminars in Immunopathology, 2015Co-Authors: Catharina M Muldersmanders, Anna SimonAbstract:Mevalonate kinase deficiency or hyper-IgD syndrome is a hereditary autoinflammatory syndrome caused by mutations in the Mevalonate kinase gene. In this review, we will discuss new findings in this disorder that have been published in the last 2 years. This includes new insights into pathophysiology, treatment, and the clinical phenotype linked to the genetic defect.
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Mevalonate kinase deficiency: Evidence for a phenotypic continuum
Neurology, 2004Co-Authors: Anna Simon, Hubertus P. H. Kremer, Ron A. Wevers, Hans Scheffer, J.g.n. De Jong, J.w.m. Van Der Meer, J.p.h. DrenthAbstract:Both mevalonic aciduria, characterized by psychomotor retardation, cerebellar ataxia, recurrent fever attacks, and death in early childhood, and hyper-immunoglobulin D (hyper-IgD) syndrome, with recurrent fever attacks without neurologic symptoms, are caused by a functional deficiency of Mevalonate kinase. In a systematic review of known Mevalonate kinase-deficient patients, the authors identified five adults with phenotypic overlap between these two syndromes, which argues for a continuous spectrum of disease. Mevalonate kinase deficiency should be considered in adult patients with fitting neurologic symptoms, with or without periodic fever attacks.
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molecular analysis of the Mevalonate kinase gene in a cohort of patients with the hyper igd and periodic fever syndrome its application as a diagnostic tool
Annals of Internal Medicine, 2001Co-Authors: Anna Simon, J.w.m. Van Der Meer, Laurence Cuisset, Marie-françoise Vincent, Marc Delpech, S D Van Der Veldevisser, J.p.h. DrenthAbstract:Background: The hyper-IgD and periodic fever syndrome (HIDS) is characterized by recurrent attacks of fever, abdominal distress, and arthralgia and is caused by Mevalonate kinase mutations. Objective: To ascertain the role of Mevalonate kinase and the usefulness of molecular diagnosis in HIDS. Design: Cross-sectional study. Setting: The international Nijmegen HIDS registry. Patients: 54 patients from 41 families who met the clinical criteria for HIDS. Measurements: Clinical symptoms and signs, immunoglobulin concentration, leukocyte count, erythrocyte sedimentation rate, mutation analysis, and Mevalonate kinase enzyme activity assay. Results: There were two groups of patients: 41 patients with Mevalonate kinase mutations (classic-type HIDS) and 13 patients without mutations (variant-type HIDS). Patients with classic-type HIDS had a lower Mevalonate kinase enzyme activity, a higher IgD level, and more additional symptoms with attacks. The IgD level did not correlate with disease severity, Mevalonate kinase enzyme activity, or genotype. Conclusion: Genetic heterogeneity exists among patients with a clinical diagnosis of HIDS.
