Hydroxy Unsaturated Fatty Acids Research Articles

Glycosylated 24-membered lactones and unsaturated fatty acids from cold-seep-derived Bacillus sp. HDN 20-1259

One new glycosylated macrolactin compound, 6′-O-succinyl methyl ester macrolactin O (1), two new hydroxy unsaturated fatty acids (3 and 4), together with three known compounds succinyl macrolactin O (2), macrolactin O and F (5 and 6), were isolated from the liquid culture of Bacillus sp. HDN20-1259. The chemical structures of 1–6 were elucidated by extensive NMR, MS, ECD, Mosher's method and thiocarbamoyl-thiazolidine derivatization with reversed-phase HPLC analysis. Compounds 1, 2, 5, and 6 showed extensive antibacterial activity against Bacillus cereus, Staphylococcus aureus, and Escherichia coli, among which 1 and 2 showed antibacterial activity against Staphylococcus aureus with MIC value of 50 µg/ mL. This is the first report of secondary metabolites obtained from cold-seep-derived Bacillus sp..

Antifungal cultures and metabolites of lactic acid bacteria for use in dairy fermentations

Fungal spoilage limits the shelf life of fermented dairy products. To address the problem, this study explores the potential of lactic acid bacteria as antifungal adjunct cultures in dairy matrices. Strains of lactic acid bacteria (113) representing 19 species were screened for their activity against Penicillium caseifulvum, Aspergillus clavatus and Mucor racemosus in modified MRS medium, milk, and yogurt. Strains of Lactiplantibacillus plantarum, Furfurilactobacillus milii, and Lentilactobacillus parabuchneri inhibited the growth of mycelial fungi. The inhibitory effects of lactic acid bacteria against yeasts were also determined in yogurt with Candida sake, Saccharomyces bayanus, and Torulaspora delbrueckii as challenge strains. The inhibition of yeasts by lactic acid bacteria was strain-specific and unrelated to the activity towards mycelial fungi. Organic acids and hydroxy fatty acids were quantified by liquid chromatograph coupled with refractive index detector and tandem mass spectrometry, respectively. Principal component analysis indicated 10-OH 18: 1 fatty acids and acetate are the main antifungal metabolites and explained over 50 % of the antifungal activity. The correlation analysis of metabolites and mold-free shelf life of milk and yogurt confirmed the role of these compounds. The genomic study analysed genes related to the production of major antifungal metabolites and predicted the formation of 1,2-propanediol and acetate but not of hydroxy unsaturated fatty acids. The findings provide new perspectives on the selection of antifungal strains, the characterization of antifungal metabolites and the exploration of antifungal mechanisms among different species.

Bioactivities of algicidal C18 hydroxy unsaturated fatty acid isolated from the red alga Tricleocarpa jejuensis and its synthesized propargylic derivative

(±)-(E)-12-hydroxyoctadec-10-enoic acid (compound A) was isolated from the red alga Tricleocarpa jejuensis in our previous study as a potent algicidal compound against red tide microalga Chattonella antiqua (Ochrophyta, Raphidophyceae). Interestingly, its propargylic derivative, 12-hydroxyoctadec-10-ynoic acid (compound B), which was obtained as a synthetic intermediate of compound A, showed an even more extensive algicidal activity. In this study, the effects of compound A and B on the major causative species of harmful algal blooms (HABs) such as Chattonella marina (Ochrophyta, Raphidophyceae), Heterocapsa circularisquama, and Karenia mikimotoi (Miozoa, Dinophyceae) in addition to C. antiqua were investigated. Both compounds exhibited toxic effects on these red tide flagellates in a concentration dependent manner with LC50 < 10 μg/mL, and the activities of compound B were much stronger than compound A. Zooplankton rotifer (Brachionys plicatilis) was relatively resistant to the compounds, and the lethal effects of H. circularisquama and K. mikimotoi on rotifers were reduced in the presence of compound A and B, suggesting their potential usage in the mitigation strategy for HABs. Consistent with the toxicities on the HAB species, compound B showed stronger cytotoxicity on HeLa, XC, and U937 cells than A. Since compound B but not compound A showed haemolytic activity on rabbit erythrocytes, specific action of compound B on cell membrane may be responsible for the potent cytotoxicity. Furthermore, compound B exhibited higher antibacterial effect on Staphylococcus aureus than compound A, while both were not effective on Enchiridia coli. Our results suggest that compound A and B are promising multifunctional candidates with potential to develop not only as anti-red tide microalgae but also as tumor cell-killing and antibacterial agents. This is the first report indicating that replacing a double bond in the hydroxy unsaturated fatty acid with a triple bond results in much augmentation of the bioactivities.

Investigating the potential of unsaturated fatty acids as antifungal crop protective agents

Pathogenic fungi cause significant yield losses and quality reductions to many crops including canola, wheat, and barley. Toxic metabolites produced by fungal pathogens, along with excessive application of synthetic fungicides, can also pose risks to human and livestock health. Hydroxy unsaturated fatty acids (HUFAs) are novel alternatives to commonly used fungicides. Here, the antifungal activities of two HUFAs, coriolic acid (CA) and ricinoleic acid (RA), were assessed in vitro and in planta for their activity against the important phytopathogens Fusarium graminearum Schwabe, Pyrenophora tritici-repentis (Died.) Drechsler, Pyrenophora teres f. teres Drechsler, Sclerotinia sclerotiorum (Lib.) de Bary, Leptosphaeria maculans Ces. &amp; De Not., and Aspergillus niger Tiegh. on selected media, monocots or dicots. The results in vitro indicated that both CA and RA showed the strongest inhibitory activity against L. maculans and A. niger, but their activities varied with different fungi. On wheat and barley, CA but not RA reduced disease severity caused by Pyrenophora spp.; on canola, treatment with high levels of CA and RA led to oxidative damage of the plant tissues, and treatment with low concentrations of CA and RA did not reduce disease severity caused by L. maculans or S. sclerotiorum on canola. Our findings suggest that the utility of HUFAs in reducing disease severity caused by pathogenic fungi depends on the dosage and the plant and fungus targeted. High concentrations of HUFA can be phytotoxic on certain plants. In addition to their direct antifungal properties, additional mechanisms may be involved in the disease reduction of CA, suggesting the need for further evaluation of its potential use in crop protection.

Structure-function relationships of antifungal monohydroxy unsaturated fatty acids (HUFA) of plant and bacterial origin

This study investigated the relationships between the structures of hydroxy unsaturated fatty acids (HUFA) and their antifungal activities. Structurally diverse HUFA, including four monohydroxy-18:1 isomers, two monohydroxy 18:2 isomers and two monohydroxy 18:2 isomers were extracted from seeds of plants (Coriaria nepalensis, Thymus vulgaris, Mallotus philippensis and Dimorphotheca sinuata) for which information was available on PlantFAdb database, and from culture supernatants of lactobacilli. They were purified by high-speed counter current chromatography (HSCCC) and identified by LC-MS/MS. The minimum inhibitory concentrations of HUFA were tested against a panel of five yeasts and five mycelial fungi. The membrane phase changes under HUFA treatment and the content of ergosterol were both measured to differentiate HUFA-sensitive and HUFA-resistant fungi. HUFA with a hydroxyl group near the center of the 18-carbon fatty acid chains were found to contribute strongly to HUFA antifungal activity. Antifungal HUFA targeted filamentous fungi but not yeasts. HUFA didn’t alter the overall membrane fluidity of sensitive fungi, but the most HUFA-sensitive fungi had a lower average ergosterol content compared to the resistant yeasts. This indicates the possible interaction of HUFA with fungal membrane with low sterol content, which partially support the previous proposed mode of action. Findings here provide insight on further development of HUFA application in food products.

High-Speed Counter-Current Chromatography (HSCCC) Purification of Antifungal Hydroxy Unsaturated Fatty Acids from Plant-Seed Oil and Lactobacillus Cultures.

Hydroxy unsaturated fatty acids (HUFA) can function as antifungal agents. To investigate the antifungal spectrum, that is, the scope of the in vitro fungal-inhibition activities of HUFA and their potential applications, three HUFA were produced by microbial transformation or extracted from plant-seed oils; these compounds included coriolic acid (13-hydroxy-9,11-octadecadienoic acid) from Coriaria seed oil, 10-hydroxy-12-octadecenoic acid from cultures of Lactobacillus hammesii, and 13-hydroxy-9-octadecenoic acid from cultures of Lactobacillus plantarum TMW1.460Δlah. HUFA were purified by high-speed counter-current chromatography (HSCCC), characterized by LC-MS and MS/MS, and their antifungal activities were evaluated with 15 indicator fungal strains. The HUFA had different antifungal spectra when compared with unsaturated fatty acids with comparable structures but without hydroxy groups. The inhibitory effects of HUFA specifically targeted filamentous fungi, including Aspergillus niger and Penicillium roqueforti, whereas yeasts, including Candida spp. and Saccharomyces spp., were resistant to HUFA. The findings here support the development of food applications for antifungal HUFA.

Production of 8,11-dihydroxy and 8-hydroxy unsaturated fatty acids from unsaturated fatty acids by recombinant Escherichia coli expressing 8,11-linoleate diol synthase from Penicillium chrysogenum.

Hydroxy unsaturated fatty acids can be used as antimicrobial surfactants. 8,11-Linoleate diol synthase (8,11-LDS) catalyzes the conversion of unsaturated fatty acid to 8-hydroperoxy unsaturated fatty acid, and it is subsequently isomerized to 8,11-dihydroxy unsaturated fatty acid by the enzyme. The optimal reaction conditions of recombinant Escherichia coli expressing Penicillium chrysogenum 8,11-LDS for the production of 8,11-dihydroxy-9,12(Z,Z)-octadecadienoic acid (8,11-DiHODE), 8,11-dihydroxy-9,12,15(Z,Z,Z)-octadecatrienoic acid (8,11-DiHOTrE), 8-hydroxy-9(Z)-hexadecenoic acid (8-HHME), and 8-hydroxy-9(Z)-octadecenoic acid (8-HOME) were pH 7.0, 25°C, 10 g/L linoleic acid, and 20 g/L cells; pH 6.0, 25°C, 6 g/L α-linolenic acid, and 60 g/L cells; pH 7.0, 25°C, 8 g/L palmitoleic acid, and 25 g/L cells; and pH 8.5, 30°C, 6 g/L oleic acid, and 25 g/L cells, respectively. Under these optimized conditions, the recombinant cells produced 6.0 g/L 8,11-DiHODE for 60 min, with a conversion of 60% (w/w) and a productivity of 6.0 g/L/h; 4.3 g/L 8,11-DiHOTrE for 60 min, with a conversion of 72% (w/w) and a productivity of 4.3 g/L/h; 4.3 g/L 8-HHME acid for 60 min, with a conversion of 54% (w/w) and a productivity of 4.3 g/L/h; and 0.9 g/L 8-HOME for 30 min, with a conversion of 15% (w/w) and a productivity of 1.8 g/L/h. To best of our knowledge, this is the first report on the biotechnological production of 8,11-DiHODE, 8,11-DiHOTrE, 8-HHME, and 8-HOME. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:390-396, 2017.

Isolation of cholinesterase and β-secretase 1 inhibiting compounds from Lycopodiella cernua

Three new serratene-type triterpenoids (1–3) and a new hydroxy unsaturated fatty acid (13) together with nine known compounds (4–12) were isolated from Lycopodiella cernua. The chemical structures were established using NMR, MS, and Mosher’s method. Compound 13 showed the most potent inhibitory activity against acetylcholinesterase (AChE) with an IC50 value of 0.22μM. For butyrylcholinesterase (BChE) inhibitory activity, 5 showed the most potent activity with an IC50 value of 0.42μM. Compound 2 showed the most potent activity with an IC50 of 0.23μM for BACE-1 inhibitory activity. The kinetic activities were investigated to determine the type of enzyme inhibition involved. The types of AChE inhibition shown by compounds 4, 5, and 13 were mixed; BChE inhibition by 5 was competitive, while 2 and 6 showed mixed-types. In addition, molecular docking studies were performed to investigate the interaction of these compounds with the pocket sites of AChE. The docking results revealed that the tested inhibitors 3, 4, and 13 were stably present in several pocket domains of the AChE residue.

New antimicrobial compounds from a marine-derived Bacillus sp.

In the course of our ongoing research for antimicrobial agents, we isolated five new compounds, three 24-membered macrolactones, macrolactins X-Z (1-3) and two hydroxy unsaturated fatty acids, linieodolides A (5) and B (6), together with a known metabolite, macrolactinic acid (4), from the culture broth of a marine Bacillus sp. The structures of these metabolites were determined on the basis of their spectroscopic data interpretation. Their absolute configurations were addressed by modified Mosher's method and literature data review. Compounds 1-6 showed moderate to potent inhibitory activities (8∼128 μg ml(-1)) against selected pathogenic microorganisms.

Peroxisome Proliferator-Activated Receptor .GAMMA. Ligands Isolated from Adlay Seed (Coix lacryma-jobi L. var. ma-yuen STAPF.)

Through screening for natural ligands against peroxisome proliferator-activated receptor gamma (PPARgamma) using the PPARgamma luciferase reporter assay, 6 hydroxy unsaturated fatty acids were isolated from adlay seed (Coix lacryma-jobi L. var. ma-yuen STAPF.) extracts with acetone and 70% ethanol. The structures of these compounds were determined via spectral analysis as 13-hydroxy-(9E,11E)-octadecadienoic acid (13-E,E-HODE) (1), 9-hydroxy-(10E,12E)-octadecadienoic acid (9-E,E-HODE) (2), 9-hydroxy-(10E)-octadecenoic acid (3), 10-hydroxy-(8E)-octadecenoic acid (4), 8-hydroxy-(9E)-octadecenoic acid (5), 11-hydroxy-(9Z)-octadecenoic acid (6). 9-E,E-HODE (2) exhibited the most potent PPARgamma agonist activity of the isolated hydroxy unsaturated fatty acids. 9-E,E-HODE (2) and 13-E,E-HODE (1) are the respective geometrical isomers of 9-hydroxy-(10E,12Z)-octadecadienoic acid and 13-hydroxy-(9Z,11E)-octadecadienoic acid, both of which are likely to be natural PPARgamma agonists produced in various mammalian cells, suggesting that 9-E,E-HODE may also act as PPARgamma agonist.

Phytochemical and Antimicrobial Investigation of Latex from Euphorbia Abyssinica Gmel

Phytochemical investigation of the latex of Euphorbia abyssinica Gmel (Euphorbiaceae) afforded a new hydroxy unsaturated fatty acid, 8( R)-hydroxy-dec-3( E)-en-oic acid (1), in addition to the four known compounds lupeol (2), β-sitosterol (3), oleanolic acid (4) and β-sitosterol-3- O-glucoside (5). The in vitro antibacterial and antifungal activities of the isolated compounds, as well as the total methanol extract, were studied against different micro-organisms; compound 1 displayed reasonable antifungal activities towards the tested fungi.

Fatty Acids and Sterols from Cymbopogon martinii var. Motia Roots

The hexane and methanol extracts of the roots of Cymbopogon martinii var. motia have been investigated to afford mainly fatty acids and common sterols. A new hydroxy unsaturated fatty acid, namely, 16-hydroxypentacos-14(z)-enoic acid, has also been isolated.

Production of polyhydroxy fatty acids from linoleic acid by Clavibacter sp. ALA2

AbstractHydroxy fatty acids are important industrial materials. We isolated a microbial culture, Clavibacter sp. ALA2, which converts linoleic acid to many polyhydroxy fatty acids. Structures of the products were determined as: 12,13,17‐trihydroxy‐9(Z)‐octadecenoic (THOA, main product), 12‐[5‐ethyl‐2‐tetrahydrofuranyl]‐7,12‐dihydroxy‐9(Z)‐dodecenoic (ETDDA), and 12‐[5‐ethyl‐2‐tetrahydrofuranyl]‐12‐hydroxy‐9(Z)‐dodecenoic (ETHDA) acid. The yield of THOA was 25% and the relative amount of the products were THOA/ETDDA/ETHDA =9:1.3:1. The structures of the hydroxy unsaturated fatty acids resemble those of plant self‐defense substances.

ChemInform Abstract: Production of Hydroxy Unsaturated Fatty Acids Using Crude Lipoxygenase Obtained from Infected Rice Plants.

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Production of Hydroxy Unsaturated Fatty Acids Using Crude Lipoxygenase Obtained from Infected Rice Plants

Abstract In order to explore the oxidation mode of lipoxygenase (LOX) obtained from infected rice plants, typical unsaturated fatty acids (3—8) were treated with LOX and oxygen. It was observed that ω-10 and ω-6 positions of unsaturated fatty acids were oxidized predominantly in the cases of exotic ω-6 (4 and 5) and ω-3 (7 and 8) series, respectively. In the case of endogenous fatty acids (3 and 6), oxidation at ω-6 position predominated. All the allylic alcohols obtained by reduction of the oxidation products with NaBH4 possess S-configuration.

Metabolism of Leukotriene B 4 in Cultured Hepatoma Cells

Incubation of leukotriene B 4 (LTB 4) with Hep G2 cells (a human-derived hepatoma cell line) resulted in the production of several metabolites indicative of alternative pathways of LTB 4 metabolism not previously observed in normal hepatocytes. The major extracellular LTB 4-derived metabolites were structurally identified using mass spectrometry and ancillary techniques including electrospray ionization. The major metabolite was 10 hydroxy-4,6,8,12-octadecatetraenoic acid (10-HOTE), an unexpected metabolite which lost the hydroxy group at carbon 5 from the parent LTB 4. Two other major metabolites were 3(R)-hydroxy-LTB 4 and 3(S)-hydroxy-LTB 4. The formation of these three metabolites revealed that β-oxidation from the carboxyl terminus can be a significant metabolic pathway for degradation of this hydroxy unsaturated fatty acid. The normal hepatocyte LTB 4-derived metabolite, 20-carboxy-LTB 4, was observed as only a minor product. The metabolic profile for Hep G2 cells suggests that the efficient cytochrome P-450 pathway involved in ω-oxidation in typical hepatocytes is absent in these cells. Several minor metabolites were also identified which included dihydro products resulting from metabolism by a 12-hydroxydehydrogenase/Δ 10-reductase pathway. The formation of the major metabolite reveals the operation of steps in β-oxidation of hydroxy, unsaturated fatty acids not anticipated by previously identified steps of fatty acid β-oxidation.

A new synthetic route to optically active .ALPHA.,.BETA.- and .BETA.',.GAMMA.'-unsaturated alcohols, and its application to the synthesis of a fungitoxic C-18 hydroxy unsaturated fatty acid.

A new synthetic route to optically active α, β-, β', γ'-unsaturated alcohols was established. The chiral enones (6 and 8), prepared from dimethyl malate via chiral phosphonates (4 and 5), were diastereoselectively reduced with Zn(BH4)2 to afford the 1, 3-syn derivatives (9 and 11). As an application of this 1, 3-asymmetric induction, the fungitoxic C-18 hydroxy unsaturated fatty acid isolated from stromata of Epichloe typhina was synthesized.

Four fungitoxic C-18 hydroxy unsaturated fatty acids from stromata of [formula omitted

Four fungitoxic C-18 hydroxy unsaturated fatty acids ( 1 )–( 4 ) have been isolated from stromata of Epichloe typhina . Their structures including the absolute configuration have been elucidated from spectral data.

Alkaline cleavage of hydroxy unsaturated fatty acids and derivatives. II 10‐hydroxydecanoic acid from ricinoleates and 1,10‐decanediol from ricmoleyl alcohol

AbstractThe 10‐hydroxydecanoic acid is formed in good yield when raw castor oil or methyl ricinoleate is fused with alkali in the presence of a high‐boiling unhindered primary or secondary alcohol at 185–195C bath temperature. When non‐reducing solvents or hindered alcohols are used, large amounts of sebacic acid form. Iso‐octanol (mixed isomers) is a suitable and potentially economical medium for producing high yields of 10‐hydroxydecanoic acid. Cleavage of ricinoleyl alcohol produces 1,10‐decanediol.

The effect of prostaglandins on protein and nucleic acid synthesis in a cell-free system

T6S EFFECT OF PROSTAGLAI~INS ON PROTEIN AND NDCLEIC ACID SYNTHESIS IN A CELL-FREE SYSTEM R. W. Ruddon* and J. M. Johnson Department of Pharmacology, The pniversity of Michigan Medical School Ann Arbor, Michigan (Received 20 February 1967 ; in final form 13 March 1967) THE prostaglandins are a family of hydroxy unsaturated C20 fatty acids which have been classified into an E and F aeries . Six different compounds have been isolated from various natural sources, including semen, vesicular glands, menstrual fluid, lung, brain, thymus, and iris (1) . The prostaglandins have a variety of effects on biological systems. Prostaglandin El, for example, inhibits the tone of vascular, respiratory, and reproductive smooth muscle, inhibits the mobilisation of fatty acids from adipose tissue in response to catecholaminas, and depresses the central nervous system (1,2). On the basis of present evidence it seems that the prostaglandine are not circulating hormones and that they may act intracellulary as co-enzymes or as a factor in cellular control mechanisms (1) . If this .vere true, these agents could be ezpected to affect biosynthetic mechanisms . The present investigation vas designed to examine the effects of two prostaglandina, PGEl and PGFla, on protein and nucleic acid synthesis in a cell=free system derived from E. cola B cells .