• Cerulenin is an antifungal antibiotic that inhibits fatty acid and steroid biosynthesis. (wikipedia.org)
  • It was also reported that cerulenin specifically inhibited fatty acid biosynthesis in Saccharomyces cerevisiae without having an effect on sterol formation. (wikipedia.org)
  • During lipid synthesis, ACL converts cytosolic citrate into acetyl-CoA and oxaloacetate, the essential metabolites for lipid biosynthesis, and ACC carboxylates acetyl-CoA to produce malonyl-CoA. (koreamed.org)
  • Our findings open up possibilities for the practical biosynthesis of natural pinosylvin from lignin-derived standard model monomer cinnamic acid at industrial scale. (biomedcentral.com)
  • A fatty acid coenzyme derivative which plays a key role in fatty acid oxidation and biosynthesis. (lookformedical.com)
  • 2-Fluoropalmitic acid is a synthetic inhibitor of palmitoyl-CoA formation by long chain acyl-CoA synthetase thereby inhibiting sphingosine biosynthesis and protein palmitoylation. (matreya.com)
  • Futile cycling of intermediates of fatty acid biosynthesis toward peroxisomal beta-oxidation in Saccharomyces cerevisiae. (unil.ch)
  • On the other hand, cerulenin is a known inhibitor of the FAS system but inhibition is unselective in type I and II FAS. (uni-wuerzburg.de)
  • Inhibition of triacylglycerol (TAG) synthesis via diacylglycerol acyltransferase 2 (DGAT2) antisense oligonucleotides improves liver steatosis (Yamaguchi et al. (webmedcentral.com)
  • Finally, blocking lipogenesis with fatty acid synthase inhibitors (cerulenin and C75) and siRNA-mediated silencing of SREBP1 and ATP citrate lyase (ACL) significantly attenuated GSK3 inhibition-induced senescence. (koreamed.org)
  • In the course of this, it was shown for the first time that the inhibition of fatty acid synthesis both in vitro and in vivo is associated with an aggravation of acute cell damage and increased infarct volume after cerebral ischemia. (uni-goettingen.de)
  • At the same time, inhibition of fatty acid synthesis has a negative effect on neurological recovery after cerebral ischemia. (uni-goettingen.de)
  • Although no change in the quantification of free fatty acids was detected, the inhibition of fatty acid synthesis limits the reduction potential, which in turn modulates various metabolic pathways. (uni-goettingen.de)
  • We next investigated whether the inhibition of FASN by using a specific FASN inhibitor, cerulenin, can influence growth and EMT/metastatic potential of A549CisR and H157CisR cells. (oncotarget.com)
  • After inhibition of FA synthesis, tumorigenesis was blocked, and tumors regressed in both xenograft and primary transgenic mouse models, revealing the vulnerability of MYC-induced tumors to the inhibition of lipogenesis. (stanford.edu)
  • Genomic dependent and genomic independent effects of triiodothyronine on free fatty acids (FFA) synthesis have been determined. (webmedcentral.com)
  • A fungus ( C. neoformans ) grown in three conditions: untreated, treated with a sub-lethal dose of the fatty acid synthase inhibitor NPD6433, and treated with a fluconazole. (scitechdaily.com)
  • Further experiments showed that NPD6433 and cerulenin, another fatty acid synthase inhibitor, were able to kill numerous yeast species in the culture. (scitechdaily.com)
  • This product is the inactive methyl ester of the acyl-CoA synthase inhibitor 2-fluoropalmitic acid. (matreya.com)
  • Through screening the RIKEN natural product depository (NPDepo) and identifying a specific compound, NPD6433, that inhibits fatty acid synthase, they found this approach reduced fatalities in infected laboratory worms by about 50% and may offer a promising alternative to current treatments that are becoming less effective due to increasing drug resistance. (scitechdaily.com)
  • It was the first natural product antibiotic known to inhibit lipid synthesis. (wikipedia.org)
  • The chemical composition of lipid inclusions in Bacillus megaterium was identifed in 1926 as poly(3-hydroxybutyric acid) ( Lemoigne M, Bull Soc Chim Biol 1926, 8, 770 ). (gerli.com)
  • Cerulenin, a fatty acid synthase (FASN) natural inhibitor, and Atorvastatin, a competitive inhibitor of the mevalonate pathway, have been used to test the cytotoxic effects on PDAC CSCs. (atlasofscience.org)
  • We observed a highly up-regulated fatty acid synthase (FASN) level in A549CisR and H157CisR cells compared to parental cells and the up-regulation of FASN was also detected in A549P and H157P cells after short time treatment with cisplatin, suggesting that the high level of FASN in cisplatin-resistant cells may be from the accumulated cellular responses during cisplatin-resistance developmental process. (oncotarget.com)
  • The first cerulenin derivatives were prepared by coupling 2,3-dihydrofuran to the before synthesized 1-octaniodide, followed by ring opening and oxidation in one step by chromic acid and transfer of the resulting 4-keto acid to amides to give analogues 4a-d, 4e was prepared in analogy. (uni-wuerzburg.de)
  • The following synthesis sequence starting from 12 was executed similar to that of dihydrocerulenins via the corresponding lactone (51) with the major exception of the oxidation procedure in the last step via TPAP/NMO to result in (4Z,7E)-cerulenin analogues 15a-b. (uni-wuerzburg.de)
  • It also has the related activity of stimulating fatty acid oxidation through the activation of CPT1, another enzyme normally inhibited by malonyl-CoA. (wikipedia.org)
  • Organic, monobasic acids derived from hydrocarbons by the equivalent of oxidation of a methyl group to an alcohol, aldehyde, and then acid. (lookformedical.com)
  • The work deals with the synthesis and characterization of cerulenin analogues as inhibitors of efflux pump mediated resistance of Candida albicans isolates and as inhibitors of the fatty acid synthesis enzyme KasA of Mycobacterium tuberculosis. (uni-wuerzburg.de)
  • Pharmacological testings for the synthesized substances were executed on efflux pump-resistant and -sensitive Candida albicans isolates, on the fatty acid synthesis enzyme KasA of Mycobacterium tuberculosis and on other organisms such as Leishmania major, Trypanosoma brucei brucei, Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli and Pseudomonas aeruginosa within the Sonderforschungsbereich 630. (uni-wuerzburg.de)
  • However, fatty acid synthesis, which was assessed by measuring the activities of FAS, ACC, ACL and "malic" enzyme in the liver and adipose tissues, significantly decreased in the 27-month-old Fisher 344 rats (Barakat et al. (webmedcentral.com)
  • Proteomic analysis of pancreatic cancer stem cells: Functional role of fatty acid synthesis and mevalonate pathways. (atlasofscience.org)
  • No significant tumor regression was detected at the end of cerulenin treatment, but IHC staining showed higher expression of EMT/metastasis markers in H157CisR cell-derived tumors than H157P cell-derived tumors, and showed dramatic reduction of these markers in tumor tissues of cerulenin-treated mice, confirming the in vitro results. (oncotarget.com)
  • The exposure of Saccharomyces cerevisiae cells to 13- L -hydroperoxylinoleic acid (LOOH) caused their death, the degree of which was dependent on the growth phase of the cells. (go.jp)
  • These compounds mainly include various phenolic acids, such as ferulic acid, p -coumaric acid and cinnamic acid. (biomedcentral.com)
  • From a semi-large-scale screening thus far carried out, two Epoxide compounds, Ambuic acid and Synerazol, have been found to efficiently block agr and fsr QS systems, suggesting that the Epoxide group is involved in the mode of action of these QSIs. (springeropen.com)
  • To address this notion, known natural Epoxide compounds, Cerulenin and Fosfomycin were examined for QSI activity for the agr and fsr systems in addition to in silico and SAR studies. (springeropen.com)
  • In sterol synthesis, cerulenin inhibits HMG-CoA synthetase activity. (wikipedia.org)
  • But in general conclusion, cerulenin has inhibitory effects on sterol synthesis. (wikipedia.org)
  • 2007). Suppression of the genes, which are involved in lipogenesis (ATP-citrate lyase (ACL), acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), stearoyl-CoA-desaturase 1 or sterol regulatory element-binding protein 1(SREBP-1)), reduced proliferation and survival of hepatic carcinoma cells (Calvisi et al. (webmedcentral.com)
  • Fatty acids play a pivotal role in cell metabolism - they can be generated de novo from carbon or taken up via blood stream. (uni-goettingen.de)
  • It is an amino acid derivative and an essential cofactor for fatty acid metabolism. (lookformedical.com)
  • To include the epoxide function especially with regard to the mechanism of action of cerulenin in the FAS system (considering known crystal structures of cerulenin and the KasA analogue of E. coli) tetrahydro- and dihydrocerulenin analogues were synthesized. (uni-wuerzburg.de)
  • Starting from the corresponding aldehyde, lactone 5 (tetrahydrocerulenin analogues) was obtained via two different routes A and B. Route A included the coupling of the aldehyde 1-nonanal to propiolic acid via a Grignard reaction with subsequent hydrogenation with the Lindlar catalyst under hydrogen pressure to give 5. (uni-wuerzburg.de)
  • To obtain analogues with all structural features of cerulenin including two double bonds and the epoxide function, a third pathway was chosen. (uni-wuerzburg.de)
  • A fourth class of cerulenin analogues was synthesized with the aromatic analogues 17a-e. (uni-wuerzburg.de)
  • Subsequent epoxidation with H2O2 in basic EtOH gave the aromatic cerulenin analogues 17a-e. (uni-wuerzburg.de)
  • Fatty acids play only a minor role in the central nervous system in terms of nutrition, but they are involved in the regulation of inflammation and apoptosis. (uni-goettingen.de)
  • Our findings suggested an acute reduction of fatty acid or cholesterol production that could target specific stemness features. (atlasofscience.org)
  • C ) Outer membrane vesicle (OMV) quantification of WT and Δ mlaF deletion mutants harvested at 4 hr and quantified by measuring 3-deoxy-D- manno -oct-2-ulosonic acid (Kdo) levels using the Purpald assay. (elifesciences.org)
  • GPLs were separated in solvent system containing chloroform, methanol, and acetic acid (65:25:10, v/v/v). ( C ) LSC quantification of extracted GPLs. (elifesciences.org)
  • In contrast, others have favored the concept that exaggerated insulin secretion will cause insulin resistance ( 3 , 4 ), possibly via fatty acid-mediated impairment of insulin action ( 5 - 7 ). (diabetesjournals.org)
  • Overall, it could be shown that fatty acid synthesis and its modulation plays an important role in the adaptation to hypoxic/ischemic conditions in neurons. (uni-goettingen.de)
  • Interestingly, Panc1 CSCs over-expressed enzymes involved in the pyruvate-malate cycle (citrate-pyruvate cycle) pathway, responsible for citrate transport out of the mitochondria into the cytosol where it is cleaved to oxaloacetate and acetyl-CoA, which is available then for fatty acid synthesis. (atlasofscience.org)
  • SREBP1 is a master transcription factor that regulates the expression of several lipogenic enzymes, including ATP citrate lyase (ACL), acetyl-CoA carboxylase (ACC), and fatty acid synthase (FAS) [ 11 ]. (koreamed.org)
  • We found that MYC induces SREBP1, and they collaborate to activate fatty acid (FA) synthesis and drive FA chain elongation from glucose and glutamine. (stanford.edu)
  • Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain a carboxy terminated eight carbon aliphatic structure. (lookformedical.com)
  • Amides are derived from acids by replacement of -OH by -NH2 or from ammonia by the replacement of H by an acyl group. (curehunter.com)
  • Beta-ketoacyl-ACP synthase I of Escherichia coli: nucleotide sequence of the fabB gene and identification of the cerulenin binding residue. (genebiosystems.com)
  • A saturated 14-carbon fatty acid occurring in most animal and vegetable fats, particularly butterfat and coconut, palm, and nutmeg oils. (lookformedical.com)
  • This approach targets the fungi's ability to produce fatty acids, the major component of fats. (scitechdaily.com)
  • Essential fatty acids in the vegan/total vegetarian diet People choose vegetarian/vegan diets and for many reasons, however, these diets require careful dietary planning. (atlasofscience.org)
  • Catalyzes the condensation reaction of fatty acid synthesis by the addition to an acyl acceptor of two carbons from malonyl-ACP. (genebiosystems.com)
  • We support the concept that elevated glucose and fatty acids synergize in causing toxicity in islets and other organs, a process that may be instrumental in the pleiotropic defects associated with the metabolic syndrome and type 1 and type 2 diabetes. (diabetesjournals.org)
  • citation needed] Cerulenin causes a dose-dependent decrease in HER2/neu protein levels in breast cancer cells, from 14% at 1.25 to 78% at 10 milligrams per liter, and targeting of fatty acid synthase by related drugs has been suggested as a possible treatment. (wikipedia.org)
  • Several studies have uncovered potent biological activities of 2-hydroxyoleic acid (Minerval). (gerli.com)
  • This synthesis pathway started with the formation of the benzoyl acrylamides 16a-e from benzoylacrylic acid via a mixed anhydride which was prepared with isobutylchloroformate followed by the addition of the corresponding amine. (uni-wuerzburg.de)
  • A review of fatty acid 2-hydroxylation in sphingolipid biology in connection with the nervous system and various cell types may be consulted ( Hama H , Biochim Biophys Acta 2010, 1801, 405 ). (gerli.com)
  • Both glucose and fatty acids may cause good/adaptive or evil/toxic actions on the β-cell, depending on their concentrations and the time during which they are elevated. (diabetesjournals.org)
  • We discuss here the emerging view that β-cell "glucotoxicity" is in part indirectly caused by "lipotoxicity," and that β-cell abnormalities will become particularly apparent when both glucose and circulating fatty acids are high. (diabetesjournals.org)
  • Cerulenin was chosen as the lead structure, being a substrate of the efflux pumps in Candida albicans on one hand and therefore variations on the structure could lead to a blocking of the efflux pumps as in the case of tetracycline and inhibitor 13-CPTC of the TetB efflux pump. (uni-wuerzburg.de)
  • Our research indicates that targeting fatty acid synthesis is a promising alternative therapeutic strategy for fungal infections and one which might not require tailor-made solutions for individual species. (scitechdaily.com)
  • at the same time, the maintenance of fatty acid synthesis and mevalonate pathway levels are critical contribution for survival of PDAC CSCs. (atlasofscience.org)
  • By adjusting the expression strategy, the optimized engineered strain produced pinosylvin at 153.7 ± 2.2 mg/L with an extremely high yield of 1.20 ± 0.02 mg/mg cinnamic acid in the presence of cerulenin, which is 83.9% ± 1.17 of the theoretical yield. (biomedcentral.com)