BadM Is a Transcriptional Repressor and One of Three Regulators That Control Benzoyl Coenzyme A Reductase Gene Expression in Rhodopseudomonas palustris

ABSTRACT The rate-limiting enzyme of anaerobic benzoate degradation by Rhodopseudomonas palustris, benzoyl coenzyme A (CoA) reductase, is highly sensitive to oxygen, and its synthesis is tightly regulated. We determined that a previously unknown gene in the benzoate gene cluster, badM, encodes a transcriptional repressor of benzoyl-CoA reductase gene expression. BadM controls gene expression from the benzoyl-CoA reductase promoter in concert with two previously described transcriptional activators.

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Regulation of 3-Hydroxy-3-methylglutaryl Coenzyme A Reductase Gene Expression in FRTL-5 Cells

Journal of Biological Chemistry ◽

10.1074/jbc.270.25.15231 ◽

1995 ◽

Vol 270 (25) ◽

pp. 15231-15236 ◽

Cited By ~ 24

Author(s):

Maurizio Bifulco§ ◽

Bruno Perillo§ ◽

Motoyasu Saji ◽

Chiara Laezza§ ◽

Idolo Tedesco§ ◽

...

Keyword(s):

Gene Expression ◽

Coenzyme A ◽

Reductase Gene ◽

Coenzyme A Reductase

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The Promoter of the Rat 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Gene Contains a Tissue-Specific Estrogen-Responsive Region

Molecular Endocrinology ◽

10.1210/mend.13.8.0333 ◽

1999 ◽

Vol 13 (8) ◽

pp. 1225-1236 ◽

Cited By ~ 20

Author(s):

Luciano Di Croce ◽

Guillermo P. Vicent ◽

Adali Pecci ◽

Giovannella Bruscalupi ◽

Anna Trentalance ◽

...

Keyword(s):

Estrogen Receptor ◽

Cell Lines ◽

Coenzyme A ◽

Cholesterol Metabolism ◽

Hmg Coa Reductase ◽

Tissue Specific ◽

Reductase Gene ◽

Responsive Element ◽

Coa Reductase ◽

Mcf 7

Abstract The isoprenoid metabolic pathway is mainly regulated at the level of conversion of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) to mevalonate, catalyzed by HMG CoA reductase. As estrogens are known to influence cholesterol metabolism, we have explored the potential regulation of the HMG CoA reductase gene promoter by estrogens. The promoter contains an estrogen-responsive element-like sequence at position −93 (termed Red-ERE), which differs from the ERE consensus by one mismatch in each half of the palindrome. A Red-ERE oligonucleotide specifically bound estrogen receptor in vitro and conferred receptor-dependent estrogen responsiveness to a heterologous promoter in all cell lines tested. However, expression of a reporter driven by the rat HMG CoA reductase promoter was induced by estrogen treatment after transient transfection into the breast cancer cell line MCF-7 cells but not in hepatic cell lines expressing estrogen receptor. Estrogen induction in MCF-7 cells was dependent on the Red-ERE and was strongly inhibited by the antiestrogen ICI 164,384. A functional cAMP-responsive element is located immediately upstream of the Red-ERE, but cAMP and estrogens inhibit each other in terms of transactivation of the promoter. Similarly, induction by estrogens was inhibited by micromolar concentrations of cholesterol, likely acting via changes in occupancy of the sterol-responsive element located 70 bp upstream of the Red-ERE. Thus, within its natural context, Red-ERE is able to mediate hormonal regulation of the HMG CoA reductase gene in tissues that respond to estrogens with enhanced cell proliferation, while it is not operative in liver cells. We postulate that this tissue-specific regulation of HMG CoA reductase by estrogens could partially explain the protective effect of estrogens against heart disease.

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Dietary Cholesterol Regulates Hepatic 3-Hydroxy-3-methylglutaryl Coenzyme A Reductase Gene Expression in Rats Primarily at the Level of Translation

Archives of Biochemistry and Biophysics ◽

10.1006/abbi.1998.0689 ◽

1998 ◽

Vol 354 (2) ◽

pp. 317-322 ◽

Cited By ~ 29

Author(s):

Christopher M. Chambers ◽

Gene C. Ness

Keyword(s):

Gene Expression ◽

Coenzyme A ◽

Dietary Cholesterol ◽

Reductase Gene ◽

Coenzyme A Reductase

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Emergence of W272C Substitution in Hmg1 in a Triazole-Resistant Isolate of Aspergillus fumigatus from a Chinese Patient with Chronic Cavitary Pulmonary Aspergillosis

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00263-21 ◽

2021 ◽

Author(s):

Tianyu Liang ◽

Xinyu Yang ◽

Ruoyu Li ◽

Ence Yang ◽

Qiqi Wang ◽

...

Keyword(s):

Amino Acid ◽

Aspergillus Fumigatus ◽

Amino Acid Substitution ◽

Coenzyme A ◽

Chinese Patient ◽

Resistant Isolate ◽

Pulmonary Aspergillosis ◽

First Case ◽

Reductase Gene ◽

Coa Reductase

Recently, mutations in the 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase gene (hmg1) have been identified to be associated with triazole resistance in Aspergillus fumigatus. Here, we describe the first case of the G929C mutation in the hmg1 gene, leading to the W272C amino acid substitution, in a triazole-resistant isolate of A. fumigatus recovered from a chronic cavitary pulmonary aspergillosis patient who failed voriconazole therapy in China.

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Light Suppresses 3-Hydroxy-3-methylglutaryl Coenzyme A Reductase Gene Expression in Arabidopsis thaliana

PLANT PHYSIOLOGY ◽

10.1104/pp.110.2.645 ◽

1996 ◽

Vol 110 (2) ◽

pp. 645-655 ◽

Cited By ~ 47

Author(s):

R. M. Learned

Keyword(s):

Gene Expression ◽

Arabidopsis Thaliana ◽

Coenzyme A ◽

Reductase Gene ◽

Coenzyme A Reductase

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2-Hydroxycyclohexanecarboxyl Coenzyme A Dehydrogenase, an Enzyme Characteristic of the Anaerobic Benzoate Degradation Pathway Used by Rhodopseudomonas palustris

Journal of Bacteriology ◽

10.1128/jb.182.10.2753-2760.2000 ◽

2000 ◽

Vol 182 (10) ◽

pp. 2753-2760 ◽

Cited By ~ 32

Author(s):

Dale A. Pelletier ◽

Caroline S. Harwood

Keyword(s):

Dehydrogenase Activity ◽

Coenzyme A ◽

Rhodopseudomonas Palustris ◽

Active Form ◽

Degradation Pathway ◽

Wild Type ◽

Cell Extracts ◽

Thauera Aromatica ◽

Benzoate Degradation ◽

Enzyme Characteristic

ABSTRACT A gene, badH, whose predicted product is a member of the short-chain dehydrogenase/reductase family of enzymes, was recently discovered during studies of anaerobic benzoate degradation by the photoheterotrophic bacterium Rhodopseudomonas palustris. Purified histidine-tagged BadH protein catalyzed the oxidation of 2-hydroxycyclohexanecarboxyl coenzyme A (2-hydroxychc-CoA) to 2-ketocyclohexanecarboxyl-CoA. These compounds are proposed intermediates of a series of three reactions that are shared by the pathways of cyclohexanecarboxylate and benzoate degradation used byR. palustris. The 2-hydroxychc-CoA dehydrogenase activity encoded by badH was dependent on the presence of NAD+; no activity was detected with NADP+ as a cofactor. The dehydrogenase activity was not sensitive to oxygen. The enzyme has apparent Km values of 10 and 200 μM for 2-hydroxychc-CoA and NAD+, respectively. Western blot analysis with antisera raised against purified His-BadH identified a 27-kDa protein that was present in benzoate- and cyclohexanecarboxylate-grown but not in succinate-grown R. palustris cell extracts. The active form of the enzyme is a homotetramer. badH was determined to be the first gene in an operon, termed the cyclohexanecarboxylate degradation operon, containing genes required for both benzoate and cyclohexanecarboxylate degradation. A nonpolar R. palustris badH mutant was unable to grow on benzoate or cyclohexanecarboxylate but had wild-type growth rates on succinate. Cells blocked in expression of the entire cyclohexanecarboxylate degradation operon excreted cyclohex-1-ene-1-carboxylate into the growth medium when given benzoate. This confirms that cyclohex-1-ene-1-carboxyl-CoA is an intermediate of anaerobic benzoate degradation by R. palustris. This compound had previously been shown not to be formed by Thauera aromatica, a denitrifying bacterium that degrades benzoate by a pathway that is slightly different from theR. palustris pathway. 2-Hydroxychc-CoA dehydrogenase does not participate in anaerobic benzoate degradation by T. aromatica and thus may serve as a useful indicator of an R. palustris-type benzoate degradation pathway.

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Enhanced Production of a Plant Monoterpene by Overexpression of the 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Catalytic Domain in Saccharomyces cerevisiae

Applied and Environmental Microbiology ◽

10.1128/aem.02987-09 ◽

2010 ◽

Vol 76 (19) ◽

pp. 6449-6454 ◽

Cited By ~ 61

Author(s):

Juan Rico ◽

Ester Pardo ◽

Margarita Orejas

Keyword(s):

Saccharomyces Cerevisiae ◽

Coenzyme A ◽

Catalytic Domain ◽

Laboratory Strain ◽

Strain Engineering ◽

Enhanced Production ◽

Wine Strain ◽

Coa Reductase ◽

Rate Limiting ◽

Coenzyme A Reductase

ABSTRACT Linalool production was evaluated in different Saccharomyces cerevisiae strains expressing the Clarkia breweri linalool synthase gene (LIS). The wine strain T73 was shown to produce higher levels of linalool than conventional laboratory strains (i.e., almost three times the amount). The performance of this strain was further enhanced by manipulating the endogenous mevalonate (MVA) pathway: deregulated overexpression of the rate-limiting 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) doubled linalool production. In a haploid laboratory strain, engineering of this key step also improved linalool yield.

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Genetic and dietary interactions in the regulation of HMG-CoA reductase gene expression.

The Journal of Lipid Research ◽

10.1016/s0022-2275(20)41435-x ◽

1992 ◽

Vol 33 (5) ◽

pp. 711-725

Author(s):

JJ Hwa ◽

S Zollman ◽

CH Warden ◽

BA Taylor ◽

PA Edwards ◽

...

Keyword(s):

Gene Expression ◽

Hmg Coa Reductase ◽

Reductase Gene ◽

Coa Reductase ◽

Dietary Interactions

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Structural and functional conservation between yeast and human 3-hydroxy-3-methylglutaryl coenzyme A reductases, the rate-limiting enzyme of sterol biosynthesis

Molecular and Cellular Biology ◽

10.1128/mcb.8.9.3797-3808.1988 ◽

1988 ◽

Vol 8 (9) ◽

pp. 3797-3808

Author(s):

M E Basson ◽

M Thorsness ◽

J Finer-Moore ◽

R M Stroud ◽

J Rine

Keyword(s):

Coenzyme A ◽

Sterol Biosynthesis ◽

New Drugs ◽

Yeast Cells ◽

Cdna Clones ◽

Hmg Coa Reductase ◽

Functional Conservation ◽

Mammalian Enzyme ◽

Coa Reductase ◽

Rate Limiting

The pathway of sterol biosynthesis is highly conserved in all eucaryotic cells. We demonstrated structural and functional conservation of the rate-limiting enzyme of the mammalian pathway, 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (HMG-CoA reductase), between the yeast Saccharomyces cerevisiae and humans. The amino acid sequence of the two yeast HMG-CoA reductase isozymes was deduced from DNA sequence analysis of the HMG1 and HMG2 genes. Extensive sequence similarity existed between the region of the mammalian enzyme encoding the active site and the corresponding region of the two yeast isozymes. Moreover, each of the yeast isozymes, like the mammalian enzyme, contained seven potential membrane-spanning domains in the NH2-terminal region of the protein. Expression of cDNA clones encoding either hamster or human HMG-CoA reductase rescued the viability of hmg1 hmg2 yeast cells lacking this enzyme. Thus, mammalian HMG-CoA reductase can provide sufficient catalytic function to replace both yeast isozymes in vivo. The availability of yeast cells whose growth depends on human HMG-CoA reductase may provide a microbial screen to identify new drugs that can modulate cholesterol biosynthesis.

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