Role of the Carbonyl Group in Thioester Chain Length Recognition by the Medium Chain Acyl-CoA Dehydrogenase

Biochemistry ◽  
1995 ◽  
Vol 34 (27) ◽  
pp. 8597-8605 ◽  
Author(s):  
Raymond C. Trievel ◽  
Rong Wang ◽  
Vernon E. Anderson ◽  
Colin Thorpe
Keyword(s):  
Carbonyl Group ◽  
Chain Length ◽  
Medium Chain ◽  
Chain Acyl

scholarly journals Transcriptome Changes in Pseudomonas putida KT2440 during Medium-Chain-Length Polyhydroxyalkanoate Synthesis Induced by Nitrogen Limitation

2020 ◽  
Vol 22 (1) ◽  
pp. 152
Author(s):  
Dorota Dabrowska ◽  
Justyna Mozejko-Ciesielska ◽  
Tomasz Pokój ◽  
Slawomir Ciesielski
Keyword(s):  
Chain Length ◽  
Nitrogen Limitation ◽  
Stringent Response ◽  
Wild Type ◽  
Pseudomonas Putida Kt2440 ◽  
Medium Chain ◽  
Environmental Stimuli ◽  
Medium Chain Length ◽  
In The Wild

Pseudomonas putida’s versatility and metabolic flexibility make it an ideal biotechnological platform for producing valuable chemicals, such as medium-chain-length polyhydroxyalkanoates (mcl-PHAs), which are considered the next generation bioplastics. This bacterium responds to environmental stimuli by rearranging its metabolism to improve its fitness and increase its chances of survival in harsh environments. Mcl-PHAs play an important role in central metabolism, serving as a reservoir of carbon and energy. Due to the complexity of mcl-PHAs’ metabolism, the manner in which P. putida changes its transcriptome to favor mcl-PHA synthesis in response to environmental stimuli remains unclear. Therefore, our objective was to investigate how the P. putida KT2440 wild type and mutants adjust their transcriptomes to synthesize mcl-PHAs in response to nitrogen limitation when supplied with sodium gluconate as an external carbon source. We found that, under nitrogen limitation, mcl-PHA accumulation is significantly lower in the mutant deficient in the stringent response than in the wild type or the rpoN mutant. Transcriptome analysis revealed that, under N-limiting conditions, 24 genes were downregulated and 21 were upregulated that were common to all three strains. Additionally, potential regulators of these genes were identified: the global anaerobic regulator (Anr, consisting of FnrA, Fnrb, and FnrC), NorR, NasT, the sigma54-dependent transcriptional regulator, and the dual component NtrB/NtrC regulator all appear to play important roles in transcriptome rearrangement under N-limiting conditions. The role of these regulators in mcl-PHA synthesis is discussed.

Role of carboxyl pendant groups of medium chain length poly(3-hydroxyalkanoate)s in biomedical temporary applications

2010 ◽  
Vol 117 (4) ◽  
pp. 1888-1896 ◽  
Author(s):  
E. Renard ◽  
L. Timbart ◽  
G. Vergnol ◽  
V. Langlois
Keyword(s):  
Chain Length ◽  
Medium Chain ◽  
Medium Chain Length

Gene delivery of medium chain acyl-coenzyme A dehydrogenase induces physiological cardiac hypertrophy and protects against pathological remodelling

2018 ◽  
Vol 132 (3) ◽  
pp. 381-397 ◽  
Author(s):  
Bianca C. Bernardo ◽  
Kate L. Weeks ◽  
Thawin Pongsukwechkul ◽  
Xiaoming Gao ◽  
Helen Kiriazis ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Coenzyme A ◽  
Healthy Adult ◽  
Capillary Density ◽  
Medium Chain ◽  
Adult Mice ◽  
Physiological Cardiac Hypertrophy ◽  
Chain Acyl ◽  
Acyl Coenzyme A

We previously showed that medium chain acyl-coenzyme A dehydrogenase (MCAD, key regulator of fatty acid oxidation) is positively modulated in the heart by the cardioprotective kinase, phosphoinositide 3-kinase (PI3K(p110α)). Disturbances in cardiac metabolism are a feature of heart failure (HF) patients and targeting metabolic defects is considered a potential therapeutic approach. The specific role of MCAD in the adult heart is unknown. To examine the role of MCAD in the heart and to assess the therapeutic potential of increasing MCAD in the failing heart, we developed a gene therapy tool using recombinant adeno-associated viral vectors (rAAV) encoding MCAD. We hypothesised that increasing MCAD expression may recapitulate the cardioprotective properties of PI3K(p110α). rAAV6:MCAD or rAAV6:control was delivered to healthy adult mice and to mice with pre-existing pathological hypertrophy and cardiac dysfunction due to transverse aortic constriction (TAC). In healthy mice, rAAV6:MCAD induced physiological hypertrophy (increase in heart size, normal systolic function and increased capillary density). In response to TAC (~15 weeks), heart weight/tibia length increased by ~60% in control mice and ~45% in rAAV6:MCAD mice compared with sham. This was associated with an increase in cardiomyocyte cross-sectional area in both TAC groups which was similar. However, hypertrophy in TAC rAAV6:MCAD mice was associated with less fibrosis, a trend for increased capillary density and a more favourable molecular profile compared with TAC rAAV6:control mice. In summary, MCAD induced physiological cardiac hypertrophy in healthy adult mice and attenuated features of pathological remodelling in a cardiac disease model.

MRI in medium-chain acyl-coenzyme a dehydrogenase deficiency: neuroimaging during the first month

2017 ◽  
Vol 30 (8) ◽  
Author(s):  
Lorenzo Figà Talamanca ◽  
Luca Pasquini ◽  
Antonio Napolitano ◽  
Daniela Longo
Keyword(s):  
Coenzyme A ◽  
Genetic Disorder ◽  
Brain Magnetic Resonance Imaging ◽  
Acid Oxidation ◽  
Medium Chain ◽  
Chain Acyl ◽  
Magnetic Resonance Imaging Mri ◽  
Acyl Coenzyme A ◽  
Mri Changes

AbstractBackground:Medium-chain acyl-coenzyme A dehydrogenase (MCAD) is the most common genetic disorder of fatty acid oxidation, which presents before the age of 2 with the onset of acute hypoketotic hypoglycemia, and is typically precipitated by stress.Case presentation:We report serial brain magnetic resonance imaging (MRI) changes, including MR spectroscopy (MRS) and diffusion weighted imaging (DWI), in a patient with a classical MCAD presentation, compared with five healthy controls.Conclusions:Through this unique case we analyze the evolution of radiological findings during the first month of illness and we highlight the pivotal role of MRI, especially DWI, in the early diagnosis of the decompensated state of the disease.

The turnover of medium-chain-length polyhydroxyalkanoates inPseudomonas putidaKT2442 and the fundamental role of PhaZ depolymerase for the metabolic balance

2010 ◽  
Vol 12 (1) ◽  
pp. 207-221 ◽  
Author(s):  
Laura Isabel de Eugenio ◽  
Isabel F. Escapa ◽  
Valle Morales ◽  
Nina Dinjaski ◽  
Beatriz Galán ◽  
...  
Keyword(s):  
Chain Length ◽  
Metabolic Balance ◽  
Medium Chain ◽  
Medium Chain Length

scholarly journals Role of PhaC Type I and Type II Enzymes during PHA Biosynthesis

Polymers ◽  
2018 ◽  
Vol 10 (8) ◽  
pp. 910 ◽  
Author(s):  
Valeria Mezzolla ◽  
Oscar D’Urso ◽  
Palmiro Poltronieri
Keyword(s):  
Chain Length ◽  
Ralstonia Eutropha ◽  
Chemical Properties ◽  
Class I ◽  
Type I ◽  
Class Iii ◽  
Short Chain Length ◽  
Medium Chain ◽  
Medium Chain Length

PHA synthases (PhaC) are grouped into four classes based on the kinetics and mechanisms of reaction. The grouping of PhaC enzymes into four classes is dependent on substrate specificity, according to the preference in forming short-chain-length (scl) or medium-chain-length (mcl) polymers: Class I, Class III and Class IV produce scl-PHAs depending on propionate, butyrate, valerate and hexanoate precursors, while Class II PhaC synthesize mcl-PHAs based on the alkane (C6 to C14) precursors. PHA synthases of Class I, in particular PhaCCs from Chromobacterium USM2 and PhaCCn/RePhaC1 from Cupriavidus necator/Ralstonia eutropha, have been analysed and the crystal structures of the C-domains have been determined. PhaCCn/RePhaC1 was also studied by X-ray absorption fine-structure (XAFS) analysis. Models have been proposed for dimerization, catalysis mechanism, substrate recognition and affinity, product formation, and product egress route. The assays based on amino acid substitution by mutagenesis have been useful to validate the hypothesis on the role of amino acids in catalysis and in accommodation of bulky substrates, and for the synthesis of PHB copolymers and medium-chain-length PHA polymers with optimized chemical properties.

scholarly journals Role of phaD in Accumulation of Medium-Chain-Length Poly(3-Hydroxyalkanoates) inPseudomonas oleovorans

2000 ◽  
Vol 66 (9) ◽  
pp. 3705-3710 ◽  
Author(s):  
Stefan Klinke ◽  
Guy de Roo ◽  
Bernard Witholt ◽  
Birgit Kessler
Keyword(s):  
Chain Length ◽  
Wild Type ◽  
Knockout Mutant ◽  
Medium Chain ◽  
Medium Chain Length ◽  
Associated Proteins ◽  
Intracellular Storage ◽  
Mutant Complementation ◽  
Mutant Cells

ABSTRACT Pseudomonas oleovorans is capable of producing poly(3-hydroxyalkanoates) (PHAs) as intracellular storage material. To analyze the possible involvement of phaD in medium-chain-length (MCL) PHA biosynthesis, we generated aphaD knockout mutant by homologous recombination. Upon disruption of the phaD gene, MCL PHA polymer accumulation was decreased. The PHA granule size was reduced, and the number of granules inside the cell was increased. Furthermore, mutant cells appeared to be smaller than wild-type cells. Investigation of MCL PHA granules revealed that the pattern of granule-associated proteins was changed and that the predominant protein PhaI was missing in the mutant. Complementation of the mutant with a phaD-harboring plasmid partially restored the wild-type characteristics of MCL PHA production and fully restored the granule and cell sizes. Furthermore, PhaI was attached to the granules of the complemented mutant. These results indicate that the phaD gene encodes a protein which plays an important role in MCL PHA biosynthesis. However, although its main effect seems to be the stabilization of MCL PHA granules, we found that the PhaD protein is not a major granule-associated protein and therefore might act by an unknown mechanism involving the PhaI protein.

scholarly journals Role of PhaC Type I and Type II Enzymes during PHA Biosynthesis

2018 ◽  
Author(s):  
Valeria Mezzolla ◽  
Oscar Fernando D'Urso ◽  
Palmiro Poltronieri
Keyword(s):  
Chain Length ◽  
Chemical Properties ◽  
Product Formation ◽  
Class I ◽  
Type I ◽  
Class Iii ◽  
Short Chain Length ◽  
Medium Chain ◽  
Medium Chain Length

PHA synthases (PhaC) are grouped into four classes based on the kinetics and mechanisms of reaction. The grouping of PhaC enzymes into four classes is dependent on substrate specificity, according to the preference in forming short chain length (scl) or medium chain length (mcl) polymers: class I, class III, and class IV produce scl-PHAs depending on propionate, butyrate, valerate and hexanoate precursors, while class II phaC synthesize mcl-PHAs based on the alkane (C6 to C14) precursors. PHA synthases of class I, in particular PhaCCs from Chromobacterium USM2 and PhaCCn/RePhaC1 from Cupriavidus necator/R. eutropha, have been analysed and the crystal structures of the C-domains have been determined. PhaCCn/RePhaC1 was also studied by small angle X-ray scattering (SAXS) analysis. Models have been proposed for dimerization, catalysis mechanism, substrate recognition and affinity, product formation and product egress route. The assays based on amino acid substitution by mutagenesis have been useful to validate the hypothesis on the role of amino acids in catalysis and in accommodation of bulky substrates, for the synthesis of PHB co-polymers and medium chain length-PHA polymers with optimized chemical properties.

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