scholarly journals Microbial Production of Conjugated Linoleic Acid and Conjugated Linolenic Acid Relies on a Multienzymatic System

Author(s):  
Ana S. Salsinha ◽  
Lígia L. Pimentel ◽  
Ana L. Fontes ◽  
Ana M. Gomes ◽  
Luis M. Rodríguez-Alcalá

SUMMARYConjugated linoleic acids (CLAs) and conjugated linolenic acids (CLNAs) have gained significant attention due to their anticarcinogenic and lipid/energy metabolism-modulatory effects. However, their concentration in foodstuffs is insufficient for any therapeutic application to be implemented. From a biotechnological standpoint, microbial production of these conjugated fatty acids (CFAs) has been explored as an alternative, and strains of the generaPropionibacterium,Lactobacillus, andBifidobacteriumhave shown promising producing capacities. Current screening research works are generally based on direct analytical determination of production capacity (e.g., trial and error), representing an important bottleneck in these studies. This review aims to summarize the available information regarding identified genes and proteins involved in CLA/CLNA production by these groups of bacteria and, consequently, the possible enzymatic reactions behind such metabolic processes. Linoleate isomerase (LAI) was the first enzyme to be described to be involved in the microbiological transformation of linoleic acids (LAs) and linolenic acids (LNAs) into CFA isomers. Thus, the availability oflaigene sequences has allowed the development of genetic screening tools. Nevertheless, several studies have reported that LAIs have significant homology with myosin-cross-reactive antigen (MCRA) proteins, which are involved in the synthesis of hydroxy fatty acids, as shown by hydratase activity. Furthermore, it has been suggested that CLA and/or CLNA production results from a stress response performed by the activation of more than one gene in a multiple-step reaction. Studies on CFA biochemical pathways are essential to understand and characterize the metabolic mechanism behind this process, unraveling all the gene products that may be involved. As some of these bacteria have shown modulation of lipid metabolismin vivo, further research to be focused on this topic may help us to understand the role of the gut microbiota in human health.

2021 ◽  
Vol 11 ◽  
Author(s):  
Boniface Pone Kamdem ◽  
Eutrophe Le Doux Kamto ◽  
Hugues Kamdem Paumo ◽  
Lebogang Maureen Katata-Seru ◽  
Dieudonné Emmanuel Pegnyemb ◽  
...  

Background: Dysphania ambrosioides (L.) Mosyakin & Clemants is an aromatic herb native to South America, but also distributed widely throughout Africa and Europe. This plant is traditionally used to treat various ailments including, pain and swellings, flu, parasitic diseases, and as analgesic, antipyretic, and wound healing. Phytochemical analyses of D. ambrosioides revealed the presence of terpenoids, flavonoids, coumarins, fatty acids and miscellaneous compounds among others, which might be responsible for its modern pharmacological actions. Objective: The present work summarizes recent developments on phytochemistry, ethnomedicinal use, pharmacology, and toxicity of D. ambrosioides. A critical assessment of the literature information of D. ambrosioides is also presented. Methods: The available information on D. ambrosioides was collected through libraries and electronic databases [Scifinder, ACS, Scielo, Science direct, Pubmed (National Library of Medicine), Wiley, Springer, PROTA, Web of Science, Google Web, Yahoo search and Google scholar] from respective inception until january 2021. Results: More than 150 compounds, including terpenoids, flavonoids, coumarins, fatty acids, and miscellaneous compounds etc.. were identified from D. ambrosioides. D. ambrosioides exhibited a wide range of pharmacological activities, including antimalarial, anti-inflammatory, antiparasitic, anticancer, insecticidal, antigiardial, among others. Metal nanoparticles synthesized from D. ambrosioides extracts presented enhanced pharmacological activities as compared to the crude plant extracts counterparts. Conclusion: D. ambrosioides is a promising medicinal plant, however, more in vivo experiments, cytotoxicity tests, and mechanisms of actions of its extracts and compounds are recommended to transubstantiate the ethnomedicinal claims of this plant into scientific rationale-based information.


2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Aditi Das ◽  
Josephine Watson ◽  
Lauren Carnevale ◽  
William Arnold

Abstract Objectives Omega-3 fatty acid derived endocannabinoids are metabolized by cytochrome P450s to form bioactive endocannabinoid epoxides that are anti-inflammatory Methods Lipidomics, LC-MS/MS, microglial cells culture, lipid synthesis, extractions, enzymology Results Cannabinoids are found in marijuana and also are produced naturally in the body from ω-3 and ω-6 fatty acids. Exocannabinoids in marijuana, are known to be responsible for some of its euphoric effects, but they also exhibit anti-inflammatory benefits. Our study revealed a cascade of enzymatic reactions that convert ω-3 fatty acids into anti-inflammatory endocannabinoid epoxides that act through the same receptors in the body as marijuana (PNAS 2017). Endocannabinoids are ligands for cannabinoid receptor 1 and 2 (CB1 and CB2). CB1 receptor agonists exhibit psychotropic properties while CB2 receptor agonists have anti-inflammatory effects. Consequently, there is a strong interest in the discovery of CB2 selective agonists to mitigate inflammatory pathologies. The work details the discovery and characterization of naturally occurring ω-3–derived endocannabinoid epoxides that are formed via enzymatic oxidation of ω-3 endocannabinoids by cytochrome P450 epoxygenases. These dual functional ω-3 endocannabinoid epoxides exhibit preference towards binding to CB2 receptor and are anti-inflammatory and vasodilatory and reciprocally modulate platelet aggregation. Some of the other regioisomers of ω-3 endocannabinoid epoxides are partial agonists of CB1 and stop tumor cell metastasis (J. Med. Chem 2018). By virtue of their physiological properties, they are expected to play important roles in neuroinflammation and pain. Conclusions This finding demonstrates how omega-3 fatty acids can produce some of the same medicinal qualities as marijuana, but without a psychotropic effect. In summary, the ω-3 endocannabinoid epoxides are found at concentrations comparable to those of other endocannabinoids and are expected to play critical roles during inflammation in vivo Funding Sources American Heart Association Scientist Development award, National Institute of Health (NIH) R01, NIH R03, USDA, National Multiple Sclerosis Society.


2012 ◽  
Vol 78 (15) ◽  
pp. 5375-5383 ◽  
Author(s):  
Nicole Lindenkamp ◽  
Elena Volodina ◽  
Alexander Steinbüchel

ABSTRACTβ-Ketothiolases catalyze the first step of poly(3-hydroxybutyrate) [poly(3HB)] biosynthesis in bacteria by condensation of two acetyl coenzyme A (acetyl-CoA) molecules to acetoacetyl-CoA and also take part in the degradation of fatty acids. During growth on propionate or valerate,Ralstonia eutrophaH16 produces the copolymer poly(3-hydroxybutyrate-co-3-hydroxyvalerate) [poly(3HB-co-3HV)]. InR. eutropha, 15 β-ketothiolase homologues exist. The synthesis of 3-hydroxybutyryl-CoA (3HB-CoA) could be significantly reduced in an 8-fold mutant (Lindenkamp et al., Appl. Environ. Microbiol. 76:5373–5382, 2010). In this study, a 9-fold mutant deficient in nine β-ketothiolase gene homologues (phaA,bktB, H16_A1713, H16_B1771, H16_A1528, H16_B0381, H16_B1369, H16_A0170, andpcaF) was generated. In order to examine the polyhydroxyalkanoate production capacity when short- or long-chain and even- or odd-chain-length fatty acids were provided as carbon sources, the growth and storage behavior of several mutants from the previous study and the newly generated 9-fold mutant were analyzed. Propionate, valerate, octanoate, undecanoic acid, or oleate was chosen as the sole carbon source. On octanoate, no significant differences in growth or storage behavior were observed between wild-typeR. eutrophaand the mutants. In contrast, during the growth on oleate of a multiple mutant lackingphaA,bktB, and H16_A0170, diminished poly(3HB) accumulation occurred. Surprisingly, the amount of accumulated poly(3HB) in the multiple mutants grown on gluconate differed; it was much lower than that on oleate. The β-ketothiolase activity toward acetoacetyl-CoA in H16ΔphaAand all the multiple mutants remained 10-fold lower than the activity of the wild type, regardless of which carbon source, oleate or gluconate, was employed. During growth on valerate as a sole carbon source, the 9-fold mutant accumulated almost a poly(3-hydroxyvalerate) [poly(3HV)] homopolyester with 99 mol% 3HV constituents.


2015 ◽  
Vol 83 (6) ◽  
pp. 2453-2465 ◽  
Author(s):  
Carole Guillaume ◽  
Christine Payré ◽  
Ikram Jemel ◽  
Louise Jeammet ◽  
Sofiane Bezzine ◽  
...  

We have previously shown that secreted phospholipases A2(sPLA2s) from animal venoms inhibit thein vitrodevelopment ofPlasmodium falciparum, the agent of malaria. In addition, the inflammatory-type human group IIA (hGIIA) sPLA2circulates at high levels in the serum of malaria patients. However, the role of the different human sPLA2s in host defense againstP. falciparumhas not been investigated. We show here that 4 out of 10 human sPLA2s, namely, hGX, hGIIF, hGIII, and hGV, exhibit potentin vitroanti-Plasmodiumproperties with half-maximal inhibitory concentrations (IC50s) of 2.9 ± 2.4, 10.7 ± 2.1, 16.5 ± 9.7, and 94.2 ± 41.9 nM, respectively. Other human sPLA2s, including hGIIA, are inactive. The inhibition is dependent on sPLA2catalytic activity and primarily due to hydrolysis of plasma lipoproteins from the parasite culture. Accordingly, purified lipoproteins that have been prehydrolyzed by hGX, hGIIF, hGIII, and hGV are more toxic toP. falciparumthan native lipoproteins. However, the total enzymatic activities of human sPLA2s on purified lipoproteins or plasma did not reflect their inhibitory activities onP. falciparum. For instance, hGIIF is 9-fold more toxic than hGV but releases a lower quantity of nonesterified fatty acids (NEFAs). Lipidomic analyses of released NEFAs from lipoproteins demonstrate that sPLA2s with anti-Plasmodiumproperties are those that release polyunsaturated fatty acids (PUFAs), with hGIIF being the most selective enzyme. NEFAs purified from lipoproteins hydrolyzed by hGIIF were more potent at inhibitingP. falciparumthan those from hGV, and PUFA-enriched liposomes hydrolyzed by sPLA2s were highly toxic, demonstrating the critical role of PUFAs. The selectivity of sPLA2s toward low- and high-density (LDL and HDL, respectively) lipoproteins and their ability to directly attack parasitized erythrocytes further explain their anti-Plasmodiumactivity. Together, our findings indicate that 4 human sPLA2s are active againstP. falciparumin vitroand pave the way to future investigations on theirin vivocontribution in malaria pathophysiology.


2003 ◽  
Vol 90 (3) ◽  
pp. 625-634 ◽  
Author(s):  
M. Blümmel ◽  
A. Karsli ◽  
J. R. Russell

The efficiency of rumen microbial production (EMP)in vitroandin vivowas examined for three roughages (lucerne (Medicago sativaL.) hay, oat (Avenia sativaL.)–berseem clover (Trifolium alexandrinumcultivar BigBee) hay and maize (Zea maysL.) crop residue (MCR)) and for five isonitrogenous (106 g crude protein (N × 6·25)/kg) diets formulated from lucerne hay, oat–berseem clover hay, MCR, soya-bean meal and maize grain to provide degradable intake protein for the production of 130 g microbial protein/kg total digestible nutrients. EMPin vivowas determined by intestinal purine recovery in sheep and ranged from 240 to 360 g microbial biomass/kg organic matter truly degraded in MCR and in one of the diets respectively (P<0·05). EMPin vitrowas estimated by the substrate degraded: gas volume produced thereby (termed partitioning factor, PF (mg/ml)) at times of estimated peak microbial production and after 16·0 and 24·0h of incubation. For the diets, PF values were significantly related to EMPin vivoat peak microbial production (P= 0·04), but not after 16·0 (P= 0·08) and 24·0h (P= 0·66). For roughages, PF values were significantly related to EMPin vivoonly when measured after 16·0 h (P= 0·04). For MCR and diets, a close non-linear relationship was found between PF values at peak microbial production and EMPin vivo(R20·99,P<0·0001) suggesting a maximum EMPin vivoof 0·39. Low gas production per unit substrate degraded (high PF) was associated with high EMPin vivo.Thein vitrostudy of the products of fermentation, short-chain fatty acids, gases and microbial biomass (by purine analysis) after 16·0h of incubation showed very strong relationships (R2≥ 0·89,P<0·0001) between short-chain fatty acids, gases and gravimetrically measured apparent degradability. Except for maize grain, the true degradability of organic matter estimated by neutral-detergent solution treatment agreed with the sum of the products of fermentation (R20·81,P=0·0004). After 16·0h of incubation, the synergistic effects of diet ingredient on diets were greater for microbial biomass (18%) than for short-chain fatty acids and gas production (7 %). It is concluded that measurement of gas production only gives incomplete information about fodder quality; complementation of gas measurements by true degradability measurements is recommended.


1971 ◽  
Vol 26 (03) ◽  
pp. 488-492 ◽  
Author(s):  
Th B. Tschopp ◽  
H.-R Baumgartner ◽  
A Studer

SummaryIn rabbits and cats Congo red administered intravenously causes severe thrombocytopenia and ultrastructural alterations of platelets and leucocytes, similar to those produced by some fatty acids and endotoxin. Transient leucopenia is followed by leucocytosis. In contrast, incubation of Congo red in citrated blood or platelet rich plasma has no effect. Therefore, an indirect mechanism is postulated to explain the in vivo effect of Congo red.


Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 92-OR ◽  
Author(s):  
WEI HUANG ◽  
YONG XU ◽  
YOUHUA XU ◽  
LUPING ZHOU ◽  
CHENLIN GAO

2017 ◽  
Vol 68 (9) ◽  
pp. 2196-2203 ◽  
Author(s):  
Mara Crisan ◽  
Gheorghe Maria

Novel coupled enzymatic systems reported important applications in the industrial bio-catalysis. Multi-enzymatic reactions can successfully replace complex chemical syntheses, using milder reaction conditions, and generating less waste. For such systems acting simultaneously, the model-based engineering calculations (design, reactor operation optimization) are difficult tasks, because they must account for interacting reactions, differences in enzymes optimal activity domains and deactivation kinetics. The determination of the optimal operating mode (enzyme ratios, enzyme feeding policy, temperature, pH) often turns into a difficult multi-objective optimization problem with multiple constraints to be solved for every particular system. The paper focuses on applying a modular screening procedure that can identify the optimal operating policy of an enzymatic reactor, which minimizes the enzyme consumption, given the process kinetic model, and an imposed production capacity. Following an optimization procedure, the process effectiveness is evaluated in a systematic approach, by including simple batch reactor (BR), batch with intermittent addition of the key-enzyme following certain optimal policies (BRP). Exemplification is made for the case of the enzymatic reduction of D-fructose to mannitol by using suspended MDH (mannitol dehydrogenase) and NADH (Nicotinamide adenine dinucleotide) cofactor, with the in-situ continuous regeneration of the cofactor by the expense of formate degradation in the presence of suspended FDH (Formate dehydrogenase).


Coronaviruses ◽  
2020 ◽  
Vol 01 ◽  
Author(s):  
Ashraf Talaat Youssef

The pandemic of COVID-19 had started in Wuhan city china in late 2019 with a subsequent worldwide spread. The viral infection can seriousely affect multiple organs mainly lungs, kidneys, heart, liver and brain and may lead to respiratory, renal, cardiac or hepatic failure.Vascular thrombosis of unexplained mechanism that may lead to widespread blood clots in multiple organs and cytokine storms that result of overstimulation of the immune system subsequent of lung damage may lead to sudden decompensation due to hypotension and more damage to liver, kidney, brain or lungs.Until now no drug had proved efficient in getting rid of the problem and controlling the pandemic mainly depends on preventive measures.Many preventive measures can be considered to prevent the worldwide spread of viral transmission. Polyunsaturated long chain fatty acids (PUFAs) and the medium chain saturated fatty acids (MCSFAs) and their corresponding monoglycerides had high antiviral activities against the enveloped viruses which reach to more than 10,000 -fold reduction in the viral titres in vitro and in vivo after testing of its gastric aspirate, and can contribute to the systemic immunity against the enveloped viruses.


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