抗真菌聚酮化合物安布罗霉素作用于高渗甘油（HOG）途径。
The antifungal polyketide ambruticin targets the HOG pathway.
作者信息
Vetcher Leandro, Menzella Hugo G, Kudo Toshiaki, Motoyama Takayuki, Katz Leonard
机构信息
Kosan Biosciences Inc, Hayward, CA 94545, USA.
出版信息
Antimicrob Agents Chemother. 2007 Oct;51(10):3734-6. doi: 10.1128/AAC.00369-07. Epub 2007 Aug 13.
Abstract
The polyketide ambruticin is an attractive candidate for drug development as an antifungal agent, but its mechanism of action has not yet been elucidated. Here we present evidence that ambruticin exerts its effect by targeting HOG, the osmotic stress control pathway, through Hik1, a group III histidine kinase.
摘要
聚酮化合物安布罗霉素作为一种抗真菌药物，是药物开发的一个有吸引力的候选物，但其作用机制尚未阐明。在此，我们提供证据表明，安布罗霉素通过III型组氨酸激酶Hik1靶向渗透胁迫控制途径HOG发挥其作用。
相似文献
1
The antifungal polyketide ambruticin targets the HOG pathway.
Antimicrob Agents Chemother. 2007 Oct;51(10):3734-6. doi: 10.1128/AAC.00369-07. Epub 2007 Aug 13.
2
Calcofluor antifungal action depends on chitin and a functional high-osmolarity glycerol response (HOG) pathway: evidence for a physiological role of the Saccharomyces cerevisiae HOG pathway under noninducing conditions.
J Bacteriol. 2000 May;182(9):2428-37. doi: 10.1128/JB.182.9.2428-2437.2000.
3
A novel functional assay for fungal histidine kinases group III reveals the role of HAMP domains for fungicide sensitivity.
J Biotechnol. 2012 Jan;157(1):268-77. doi: 10.1016/j.jbiotec.2011.09.017. Epub 2011 Sep 22.
4
The group III two-component histidine kinase of filamentous fungi is involved in the fungicidal activity of the bacterial polyketide ambruticin.
Appl Environ Microbiol. 2009 Jan;75(1):127-34. doi: 10.1128/AEM.00993-08. Epub 2008 Nov 14.
5
Stimulation of the yeast high osmolarity glycerol (HOG) pathway: evidence for a signal generated by a change in turgor rather than by water stress.
FEBS Lett. 2000 Apr 21;472(1):159-65. doi: 10.1016/s0014-5793(00)01445-9.
6
In vitro studies with ambruticin, a new antifungal antibiotic.
Antimicrob Agents Chemother. 1978 Jul;14(1):99-104. doi: 10.1128/AAC.14.1.99.
7
Overexpression of the CORVET complex alleviates the fungicidal effects of fludioxonil on the yeast expressing hybrid histidine kinase 3.
J Biol Chem. 2019 Jan 11;294(2):461-475. doi: 10.1074/jbc.RA118.004736. Epub 2018 Nov 16.
8
Augmenting the Activity of Monoterpenoid Phenols against Fungal Pathogens Using 2-Hydroxy-4-methoxybenzaldehyde that Target Cell Wall Integrity.
Int J Mol Sci. 2015 Nov 10;16(11):26850-70. doi: 10.3390/ijms161125988.
9
An Os-1 family histidine kinase from a filamentous fungus confers fungicide-sensitivity to yeast.
Curr Genet. 2005 May;47(5):298-306. doi: 10.1007/s00294-005-0572-6. Epub 2005 Mar 18.
10
Chemosensitization prevents tolerance of Aspergillus fumigatus to antimycotic drugs.
Biochem Biophys Res Commun. 2008 Jul 18;372(1):266-71. doi: 10.1016/j.bbrc.2008.05.030. Epub 2008 May 16.
引用本文的文献
1
Genetic engineering of Sorangium cellulosum reveals hidden enzymology in myxobacterial natural product biosynthesis.
Nat Commun. 2025 Aug 27;16(1):7996. doi: 10.1038/s41467-025-63441-y.
2
Total Synthesis of Jerangolid B via sp-sp Stille Coupling.
Org Lett. 2025 Jul 18;27(28):7719-7726. doi: 10.1021/acs.orglett.5c02569. Epub 2025 Jul 5.
3
The Corey-Seebach Reagent in the 21st Century: A Review.
Molecules. 2023 May 26;28(11):4367. doi: 10.3390/molecules28114367.
4
Myxobacterial Outer Membrane β-1,6-Glucanase Induced the Cell Death of Fusarium oxysporum by Destroying the Cell Wall Integrity.
Appl Environ Microbiol. 2023 Jan 31;89(1):e0123622. doi: 10.1128/aem.01236-22. Epub 2023 Jan 5.
5
Current Landscape of Coccidioidomycosis.
J Fungi (Basel). 2022 Apr 17;8(4):413. doi: 10.3390/jof8040413.
6
Enantioselective Total Synthesis of the Putative Biosynthetic Intermediate Ambruticin J.
Chemistry. 2021 Aug 2;27(43):11126-11131. doi: 10.1002/chem.202100975. Epub 2021 May 27.
7
The Future of Antifungal Drug Therapy: Novel Compounds and Targets.
Antimicrob Agents Chemother. 2021 Jan 20;65(2). doi: 10.1128/AAC.01719-20.
8
Cytochrome P450 Monooxygenase CYP139 Family Involved in the Synthesis of Secondary Metabolites in 824 Mycobacterial Species.
Int J Mol Sci. 2019 May 31;20(11):2690. doi: 10.3390/ijms20112690.
9
Uncertainty surrounding the mechanism and safety of the post-harvest fungicide fludioxonil.
Food Chem Toxicol. 2019 Jan;123:561-565. doi: 10.1016/j.fct.2018.11.037. Epub 2018 Nov 17.
10
Encodes a Fungal Cytochrome P450 Essential for Survival in Macrophages.
mSphere. 2018 Mar 21;3(2). doi: 10.1128/mSphere.00056-18. eCollection 2018 Mar-Apr.
本文引用的文献
1
Efficacy of ambruticin analogs in a murine model of coccidioidomycosis.
Antimicrob Agents Chemother. 2006 Oct;50(10):3467-9. doi: 10.1128/AAC.00670-06.
2
Efficacy of ambruticin analogs in a murine model of invasive pulmonary aspergillosis.
Antimicrob Agents Chemother. 2006 Oct;50(10):3464-6. doi: 10.1128/AAC.00558-06.
3
Identification of OS-2 MAP kinase-dependent genes induced in response to osmotic stress, antifungal agent fludioxonil, and heat shock in Neurospora crassa.
Fungal Genet Biol. 2007 Mar;44(3):208-18. doi: 10.1016/j.fgb.2006.08.003. Epub 2006 Sep 20.
4
Comparative analysis of HOG pathway proteins to generate hypotheses for functional analysis.
Curr Genet. 2006 Mar;49(3):152-65. doi: 10.1007/s00294-005-0039-9. Epub 2006 Feb 9.
5
An Os-1 family histidine kinase from a filamentous fungus confers fungicide-sensitivity to yeast.
Curr Genet. 2005 May;47(5):298-306. doi: 10.1007/s00294-005-0572-6. Epub 2005 Mar 18.
6
Characterization of mutations in the two-component histidine kinase gene AbNIK1 from Alternaria brassicicola that confer high dicarboximide and phenylpyrrole resistance.
Curr Genet. 2005 Apr;47(4):234-43. doi: 10.1007/s00294-005-0568-2. Epub 2005 Mar 12.
7
A two-component histidine kinase of the rice blast fungus is involved in osmotic stress response and fungicide action.
Fungal Genet Biol. 2005 Mar;42(3):200-12. doi: 10.1016/j.fgb.2004.11.002. Epub 2005 Jan 5.
8
Cloning and characterization of the histidine kinase gene Dic1 from Cochliobolus heterostrophus that confers dicarboximide resistance and osmotic adaptation.
Mol Genet Genomics. 2004 Mar;271(2):228-36. doi: 10.1007/s00438-003-0974-4. Epub 2004 Jan 30.
9
Whole-genome analysis of two-component signal transduction genes in fungal pathogens.
Eukaryot Cell. 2003 Dec;2(6):1151-61. doi: 10.1128/EC.2.6.1151-1161.2003.
10
Dicarboximide resistance in field isolates of Alternaria alternata is mediated by a mutation in a two-component histidine kinase gene.
Fungal Genet Biol. 2004 Jan;41(1):102-8. doi: 10.1016/j.fgb.2003.09.002.
Zotero 插件