acetyl coenzyme a
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2022 ◽  
Vol 119 (2) ◽  
pp. e2113853119
Author(s):  
Christian Schöne ◽  
Anja Poehlein ◽  
Nico Jehmlich ◽  
Norman Adlung ◽  
Rolf Daniel ◽  
...  

The reductive acetyl-coenzyme A (acetyl-CoA) pathway, whereby carbon dioxide is sequentially reduced to acetyl-CoA via coenzyme-bound C1 intermediates, is the only autotrophic pathway that can at the same time be the means for energy conservation. A conceptually similar metabolism and a key process in the global carbon cycle is methanogenesis, the biogenic formation of methane. All known methanogenic archaea depend on methanogenesis to sustain growth and use the reductive acetyl-CoA pathway for autotrophic carbon fixation. Here, we converted a methanogen into an acetogen and show that Methanosarcina acetivorans can dispense with methanogenesis for energy conservation completely. By targeted disruption of the methanogenic pathway, followed by adaptive evolution, a strain was created that sustained growth via carbon monoxide–dependent acetogenesis. A minute flux (less than 0.2% of the carbon monoxide consumed) through the methane-liberating reaction remained essential, indicating that currently living methanogens utilize metabolites of this reaction also for anabolic purposes. These results suggest that the metabolic flexibility of methanogenic archaea might be much greater than currently known. Also, our ability to deconstruct a methanogen into an acetogen by merely removing cellular functions provides experimental support for the notion that methanogenesis could have evolved from the reductive acetyl-coenzyme A pathway.


2022 ◽  
Author(s):  
Peng Zhou ◽  
Wenchang Li ◽  
Jianyong Lan ◽  
Tingshun Zhu

Abstract Oxidative carbene organocatalysis, inspired from Vitamin B1 catalyzed oxidative activation from pyruvate to acetyl coenzyme A, have been developed as a versatile synthetic method. To date, the α-, β-, γ-, δ- and carbonyl carbons of (unsaturated)aldehydes have been successfully activated via oxidative N-heterocyclic carbene (NHC) organocatalysis. In comparison with chemical redox or photoredox methods, electroredox methods, although widely used in mechanistic study, were much less studied in NHC catalyzed organic synthesis. Herein, an electroredox NHC organocatalysis system with iodine cocatalyst was developed. With the help of non-uniform distribution of electrolysis system, NHC and iodine, which was normally not compatible in chemical reaction, cooperated well in the electrochemical system. This cocatalyst system provided general solutions for electrochemical single-electron-transfer (SET) oxidation of Breslow intermediate towards versatile transformations. Radical clock experiment and cyclic voltammetry results suggested an anodic radical coupling pathway.


2021 ◽  
Author(s):  
Keely E.A Oldham ◽  
Erica J Prentice ◽  
Emma L Summers ◽  
Joanna L Hicks

Serine acetyltransferase (SAT) catalyzes the first step in the two-step pathway to synthesize L-cysteine in bacteria and plants. SAT synthesizes O-acetylserine from substrates L‑serine and acetyl coenzyme A and is a key enzyme for regulating cellular cysteine levels by feedback inhibition of L-cysteine, and its involvement in the cysteine synthase complex. We have performed extensive structural and kinetic characterization of the SAT enzyme from the antibiotic-resistant pathogen Neisseria gonorrhoeae. Using X-ray crystallography, we have solved the structures of NgSAT with the non-natural ligand, L-malate (present in the crystallization screen) to 2.01 Å and with the natural substrate L-serine (2.80 Å) bound. Both structures are hexamers, with each monomer displaying the characteristic left-handed parallel β-helix domain of the acyltransferase superfamily of enzymes. Each structure displays both extended and closed conformations of the C-terminal tail.  L‑malate bound in the active site results in an interesting mix of open and closed active site conformations, exhibiting a structural change mimicking the conformation of cysteine (inhibitor) bound structures from other organisms. Kinetic characterization shows competitive inhibition of L-cysteine with substrates L-serine and acetyl coenzyme A. The SAT reaction represents a key point for the regulation of cysteine biosynthesis and controlling cellular sulfur due to feedback inhibition by L-cysteine and formation of the cysteine synthase complex. Data presented here provide the structural and mechanistic basis for inhibitor design and given this enzyme is not present in humans could be explored to combat the rise of extensively antimicrobial-resistant N. gonorrhoeae.


2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 512-512
Author(s):  
Guido Kroemer

Abstract Nutrient depletion, which is one of the physiological triggers of autophagy, results in the depletion of intracellular acetyl coenzyme A (AcCoA) coupled to the deacetylation of cellular proteins. We found that there are at least 4 possibilities to mimic these effects, namely (i) the depletion of cytosolic AcCoA by interfering with its biosynthesis, (ii) the stimulation cytosolic AcCoA consumption, (iii) the inhibition of protein acetyltransferases, or (iii) the stimulation of protein deacetylases. Thus, AcCoA depleting agents, AcCoA-consuming agents, acetyltransferase inhibitors or deacetylase activators are highly efficient inducers of autophagy and reduce aging-associated diseases including diabetes, obesity, cardiac failure and failing cancer immunosurveillance. Hence, we classify them as “caloric restriction mimetics” (CRM). We have initiated the systematic search for CRMs based on their cellular effects in vitro. We built screening assays amenable to high-throughput technology for the identification of CRMs. These results will be discussed.


Weed Science ◽  
2021 ◽  
pp. 1-18
Author(s):  
Suma Basak ◽  
Douglas Goodwin ◽  
Jahangir Alam ◽  
James Harris ◽  
Jinesh D. Patel ◽  
...  

Research was conducted to evaluate acetyl-Coenzyme A carboxylase (ACCase) enzyme activity using a functional malachite green colorimetric assay previously identified as resistant to sethoxydim, and select aryloxyphenoxypropionate (FOPs) herbicides, fenoxaprop, and fluazifop. Two resistant southern crabgrass [Digitaria ciliaris (Retz.) Koeler] biotypes, R1 and R2, containing an Ile-1781-Leu amino acid substitution and previously identified as resistant to sethoxydim, pinoxaden, and fluazifop but not clethodim was utilized as the resistant chloroplastic ACCase source compared to known susceptible (S) ACCase. Dose-response studies with sethoxydim, clethodim, fluazifop-p-butyl, and pinoxaden (0.6 to 40 µM) were conducted to compare the ACCase enzyme-herbicides interaction of R1, R2, and S using the malachite green functional assay. Assay results indicated that R biotypes required more ACCase-targeting herbicides to inhibit ACCase activity compared to S. IC50 values of all four herbicides for R biotypes were consistently an order of magnitude greater than S. No sequencing differences in the carboxyltransferase domain was observed for R1 and R2, however, R2 IC50 values were greater across all herbicides. These results indicate the malachite green functional assay is effective in evaluating ACCase enzyme activity of R and S biotypes in the presence of ACCase-targeting herbicides, which can be used as a replacement for the 14C-based radiometric functional assay.


Author(s):  
Robert L. Summers ◽  
Charisse Flerida A. Pasaje ◽  
Joao P. Pisco ◽  
Josefine Striepen ◽  
Madeline R. Luth ◽  
...  

Author(s):  
Ekaterina Kozaeva ◽  
Svetlana Volkova ◽  
Marta R.A. Matos ◽  
Mariela P. Mezzina ◽  
Tune Wulff ◽  
...  

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3125
Author(s):  
Chia-Jung Li ◽  
Yi-Han Chiu ◽  
Chung Chang ◽  
Yuan-chin Ivan Chang ◽  
Jim Jinn-Chyuan Sheu ◽  
...  

Cervical squamous cell carcinoma (CESC) is one of the most common malignant tumors in women worldwide with a low survival rate. Acetyl coenzyme A synthase 2 (ACSS2) is a conserved nucleosidase that converts acetate to acetyl-CoA for energy production. Our research intended to identify the correlations of ACSS2 with clinical prognosis and tumor immune infiltration in CESC. ACSS2 is highly expressed in many tumors and is involved in the progression and metastasis of these tumors. However, it is not clear how ACSS2 affects CESC progression and immune infiltration. Analysis of the cBioPortal, GEPIA2, UALCAN, and TCGA databases showed that ACSS2 transcript levels were significantly upregulated in multiple cancer types including CESC. Quantitative RT-PCR analysis confirmed that ACSS2 expression was significantly upregulated in human cervical cancer cells. Here, we performed tissue microarray analysis of paraffin-embedded tissues from 240 cervical cancer patients recorded at FIGO/TNM cancer staging. The results showed that ACSS2 and PDL1 were highly expressed in human CESC tissues, and its expression was associated with the clinical characteristics of CESC patients. TIMER database analysis showed that ACSS2 expression in CESC was associated with tumor infiltration of B cells, CD4+ and CD8+ T cells, and cancer-associated fibroblasts (CAF). Kaplan–Meier survival curve analysis showed that CESC with high ACSS2 expression was associated with shorter overall survival. Collectively, our findings establish ACSS2 as a potential diagnostic and prognostic biomarker for CESC.


AMB Express ◽  
2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Junya Kato ◽  
Kaisei Takemura ◽  
Setsu Kato ◽  
Tatsuya Fujii ◽  
Keisuke Wada ◽  
...  

AbstractGas fermentation is one of the promising bioprocesses to convert CO2 or syngas to important chemicals. Thermophilic gas fermentation of volatile chemicals has the potential for the development of consolidated bioprocesses that can simultaneously separate products during fermentation. This study reports the production of acetone from CO2 and H2, CO, or syngas by introducing the acetone production pathway using acetyl–coenzyme A (Ac-CoA) and acetate produced via the Wood–Ljungdahl pathway in Moorella thermoacetica. Reducing the carbon flux from Ac-CoA to acetate through genetic engineering successfully enhanced acetone productivity, which varied on the basis of the gas composition. The highest acetone productivity was obtained with CO–H2, while autotrophic growth collapsed with CO2–H2. By adding H2 to CO, the acetone productivity from the same amount of carbon source increased compared to CO gas only, and the maximum specific acetone production rate also increased from 0.04 to 0.09 g-acetone/g-dry cell/h. Our development of the engineered thermophilic acetogen M. thermoacetica, which grows at a temperature higher than the boiling point of acetone (58 °C), would pave the way for developing a consolidated process with simplified and cost-effective recovery via condensation following gas fermentation.


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