- Genome Mining Discovery of Protegenins A-D, Bacterial Polyynes Involved in the Antioomycete and Biocontrol Activities of Pseudomonas protegens
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Some bacteria uniquely produce bacterial polyynes , which possess a conjugated CC bond starting with a terminal alkyne, and use them as chemical weapons against hosts and competitors. Pseudomonas protegens Cab57, a biocontrol agent against plant pathogens, has an orphan biosynthetic gene cluster for bacterial polyynes (named protegenins). In this study, the isolation, structure elucidation, and biological characterization of protegenins A-D are reported. The structures of protegenins A-D determined by spectroscopic and chemical techniques were octadecanoic acid derivatives possessing an ene-tetrayne, ene-triyne-ene, or ene-triyne moiety. The protegenins exhibited weak to strong antioomycete activity against Pythium ultimum OPU774. The deletion of proA, a protegenin biosynthetic gene, resulted in the reduction of the antioomycete activity of P. protegens. The Gac/Rsm system, a quorum sensing-like system of Pseudomonas bacteria, regulated the production of protegenins. The production profile of protegenins was dependent on the culturing conditions, suggesting a control mechanism for protegenin production selectivity. P. protegens suppressed the damping-off of cucumber seedlings caused by P. ultimum, and this protective effect was reduced in the proA-deletion mutant. Altogether, protegenins are a new class of bacterial polyynes which contribute to the antioomycete and plant-protective effects of P. protegens.
- Kai, Kenji,Murata, Kazuya,Suenaga, Mayuna
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- Enzymatic Regio- And Enantioselective C-H Oxyfunctionalization of Fatty Acids
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Directed evolution of a P450 hydroxylase (P450BSβ) achieves an engineered enzyme that is able to catalyze C-H oxyfunctionalization of fatty acids (FAs) in a highly regio- and enantioselective fashion (>20:1 Cβ/Cα and > 99% ee in all cases). The biocatalyst displays high reactivity (TON up to 1540), takes inexpensive H2O2 as oxidant, and converts C11-C18 saturated FAs as well as naturally derived unsaturated oleic and linoleic acids to optically pure β-hydroxy FAs. Merging biocatalysis with chemical transformation, we further offer a chemoenzymatic strategy to access valuable FA derivatives bearing 1,3-diol, β-amino, β-lactone, and β-lactam functionalities in either enantiomeric form. Molecular docking studies provide a rationale for the regio- and enantioselectivity of this reaction.
- Chen, Hao,Huang, Mengfei,Yan, Wenliang,Bai, Wen-Ju,Wang, Xiqing
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p. 10625 - 10630
(2021/09/02)
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- Structure of the unusual Sinorhizobium fredii HH103 lipopolysaccharide and its role in symbiosis
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Rhizobia are soil bacteria that form important symbiotic associations with legumes, and rhizobial surface polysaccharides, such as K-antigen polysaccharide (KPS) and lipopolysaccharide (LPS), might be important for symbiosis. Previously, we obtained a mutant of Sinorhizobium fredii HH103, rkpA, that does not produce KPS, a homopolysaccharide of a pseudaminic acid derivative, but whose LPS electrophoretic profile was indistinguishable from that of the WT strain. We also previously demonstrated that the HH103 rkpLMNOPQ operon is responsible for 5-acetamido-3,5,7,9-tetradeoxy-7-(3-hydroxybutyramido)-L-glyc-ero-L-manno-nonulosonic acid [Pse5NAc7(3OHBu)] production and is involved in HH103 KPS and LPS biosynthesis and that an HH103 rkpM mutant cannot produce KPS and displays an altered LPS structure. Here, we analyzed the LPS structure of HH103 rkpA, focusing on the carbohydrate portion, and found that it contains a highly heterogeneous lipid A and a peculiar core oligosaccharide composed of an unusually high number of hexuronic acids containing b-configured Pse5NAc7(3OHBu). This pseudaminic acid derivative, in its a-configuration, was the only structural component of the S. fredii HH103 KPS and, to the best of our knowledge, has never been reported from any other rhizobial LPS. We also show that Pse5NAc7(3OHBu) is the complete or partial epitope for a mAb, NB6-228.22, that can recognize the HH103 LPS, but not those of most of the S. fredii strains tested here. We also show that the LPS from HH103 rkpM is identical to that of HH103 rkpA but devoid of any Pse5NAc7(3OHBu) residues. Notably, this rkpM mutant was severely impaired in symbiosis with its host, Macroptilium atropurpureum.
- Di Lorenzo, Flaviana,Speciale, Immacolata,Silipo, Alba,Alías-Villegas, Cynthia,Acosta-Jurado, Sebastián,Rodríguez-Carvajal, Miguel-ángel,Dardanelli, Marta S.,Palmigiano, Angelo,Garozzo, Domenico,Ruiz-Sainz, José-Enrique,Molinaro, Antonio,Vinardell, José-María
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p. 10969 - 10987
(2021/01/07)
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- Synthesis of Long-Chain β-Lactones and Their Antibacterial Activities against Pathogenic Mycobacteria
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In the quest for new antibacterial agents, a series of novel long- and medium-chain mono- and disubstituted β-lactones was developed. Their activity against three pathogenic mycobacteria—M. abscessus, M. marinum, and M. tuberculosis—was assessed by the resazurin microtiter assay (REMA). Among the 16 β-lactones synthesized, only 3-hexadecyloxetan-2-one (VM005) exhibited promising activity against M. abscessus, whereas most of the β-lactones showed interesting activities against M. marinum, similar to that of the classical antibiotic, isoniazid. Regarding M. tuberculosis, six compounds were found to be active against this mycobacterium, with β-lactone VM008 [trans-(Z)-3-(hexadec-7-en-1-yl)-4-propyloxetan-2-one] being the best growth inhibitor. The promising antibacterial activities of the best compounds in this series suggest that these molecules may serve as leads for the development of much more efficient antimycobacterial agents.
- Santucci, Pierre,Dedaki, Christina,Athanasoulis, Alexandros,Gallorini, Laura,Munoz, Ana?s,Canaan, Stéphane,Cavalier, Jean-Fran?ois,Magrioti, Victoria
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p. 349 - 358
(2019/01/25)
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- Enantioselective organocatalysis-based synthesis of 3-hydroxy fatty acids and fatty γ-lactones
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3-Hydroxy fatty acids have attracted the interest of researchers, since some of them may interact with free fatty acid receptors more effectively than their non-hydroxylated counterparts and their determination in plasma provides diagnostic information regarding mitochondrial deficiency. We present here the development of a convenient and general methodology for the asymmetric synthesis of 3-hydroxy fatty acids. The enantioselective organocatalytic synthesis of terminal epoxides, starting from long chain aldehydes, is the key-step of our methodology, followed by ring opening with vinylmagnesium bromide. Ozonolysis and subsequent oxidation leads to the target products. MacMillan’s third generation imidazolidinone organocatalyst has been employed for the epoxide formation, ensuring products in high enantiomeric purity. Furthermore, a route for the incorporation of deuterium on the carbon atom carrying the hydroxy group was developed allowing the synthesis of deuterated derivatives, which may be useful in biological studies and in mass spectrometry studies. In addition, the synthesis of fatty γ-lactones, corresponding to 4-hydroxy fatty acids, was also explored.
- Bourboula, Asimina,Limnios, Dimitris,Kokotou, Maroula G.,Mountanea, Olga G.,Kokotos, George
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- Photobiocatalytic decarboxylation for olefin synthesis
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Here, we describe the combination of OleTJE with a light-driven in situ H2O2-generation system for the selective and quantitative conversion of fatty acids into terminal alkenes. The photobiocatalytic system shows clear advantages regarding enzyme activity and yield, resulting in a simple and efficient system for fatty acid decarboxylation.
- Zachos, Ioannis,Ga?meyer, Sarah Katharina,Bauer, Daniel,Sieber, Volker,Hollmann, Frank,Kourist, Robert
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supporting information
p. 1918 - 1921
(2015/02/05)
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- 2-Acety-1-(3-glycosyloxyoctadecanoyl)glycerol and dammarane triterpenes in the exudates from glandular trichome-like secretory organs on the stipules and leaves of Cerasus yedoensis
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A glycolipid, 2-acetyl-1-{3-[3,4-di-O-acetyl-β-d-glucopyranosyl-(1 → 3)-2-O-acetyl-α-l-rhamnopyranosyloxy]octadecanoyl}-sn-glycerol (1) and a dammarane triterpene, (2α,20S)-2,20-dihydroxydammar-24-en-3-one (2), along with known (20S)-20-hydroxydammar-24-en-3-one (3), were isolated from the exudates of the glandular trichome-like secretory organs in the young stipules and leaves of Cerasus yedoensis (Rosaceae).
- Asai, Teigo,Fujimoto, Yoshinori
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experimental part
p. 38 - 42
(2012/05/04)
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- Chemical Synthesis of helicobacter pylori lipopolysaccharide partial structures and their selective proinflammatory responses
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Helicobacter pylori is a common cause of gastroduodenal inflammatory diseases such as chronic gastritis and peptic ulcers and also an important factor in gastric carcinogenesis. Recent reports have demonstrated that bacterial inflammatory processes, such as stimulation with H. pylori lipopolysaccharide (LPS), initiate atherosclerosis. To establish the structures responsible for the inflammatory response of H. pylori LPS, we synthesized various kinds of lipid A structures (i.e., triacylated lipid A and Kdo-lipid A compounds), with or without the ethanolamine group at the 1-phosphate moiety, by a new divergent synthetic route. Stereoselective α-glycosylation of Kdo N-phenyltrifluoroacetimidate was achieved by use of microfluidic methods. None of the lipid A and Kdo-lipid A compounds were a strong inducer of IL-1β, IL-6, or IL-8, suggesting that H. pylori LPS is unable to induce acute inflammation. In fact, the lipid A and Kdo-lipid A compounds showed antagonistic activity against cytokine induction by E. coli LPS, except for the lipid A compound with the ethanolamine group, which showed very weak agonistic activity. On the other hand, these H. pylori LPS partial structures showed potent IL-18- and IL-12-inducing activities. IL-18 has been shown to correlate with chronic inflammation, so H. pylori LPS might be implicated in the chronic inflammatory responses induced by H. pylori. These results also indicated that H. pylori LPS can modulate the immune response: NF-κB activation through hTLR4/MD-2 was suppressed, whereas production of IL-18 and IL-12 was promoted.
- Shimoyama, Atsushi,Saeki, Akinori,Tanimura, Natsuko,Tsutsui, Hiroko,Miyake, Kensuke,Suda, Yasuo,Fujimoto, Yukari,Fukase, Koichi
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p. 14464 - 14474
(2012/02/04)
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- Enantioselective Hydrogenation of β-Keto Esters using Chiral Diphosphine-Ruthenium Complexes: Optimization for Academic and Industrial Purposes and Synthetic Applications
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Enantioselective hydrogenation using chiral complexes between atropisomeric diphosphines and ruthenium is a powerful tool for producing chiral compounds. Using a simple and straightforward in situ catalyst preparation, the conditions were optimized using molecular hydrogen for both academic and industrial purposes. This led to the best conditions and the lowest catalytic ratio required for the pressure used. Hydrogenation of various β-keto esters was efficiently performed at atmospheric and higher pressures, leading to the use of very low catalyst-substrate ratios up to 1/20,000. Asymmetric hydrogenations were used in key-steps towards the total synthesis of corynomycolic acid, Duloxetine and Fluoxetine.
- Ratovelomanana-Vidal,Girard,Touati,Tranchier,Ben Hassine,Genet
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p. 261 - 274
(2007/10/03)
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- Three new labdane diterpenoid glycosides from Conyza Blinii
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Three new labdane-type diterpenoid glycosides, blinoside A, blinoside A-15-O-[3″R-hydroxy]octadecanoate and blinoside B, together with a known labdane diterpenoid (E)-8α,15,16-trihydroxy-13-labdene, were isolated and identified from Conyza blinii.
- Su, Yanfang,Koike, Kazuo,Guo, Dean,Jia, Jinke,Liu, Jiansheng,Zheng, Junhua,Nikaido, Tamotsu
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p. 265 - 271
(2007/10/03)
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- Syntheses and biological evaluation of novel pseudomycin side-chain analogues. Part 2
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A series of aliphatic side-chain analogues of pseudomycin was synthesized and evaluated during the course of our side-chain SAR effort. We found that several of the pseudomycin side-chain analogues (e.g., 10) exhibited good in vitro activity against all t
- Chen, Shu-Hui,Sun, Xicheng,Boyer, Robert,Paschal, Jonathan,Zeckner, Doug,Current, William,Zweifel, Mark,Rodriguez, Michael
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p. 2107 - 2110
(2007/10/03)
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- Properties of unusual phospholipids. III: Synthesis, monolayer investigations and DSC studies of hydroxy octadeca(e)noic acids and diacylglycerophosphocholines derived therefrom
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Diacylglycerophosphocholines containing (R)-3-, (R)-12-, (R)-17-hydroxy octadeca(e)noic acids and the corresponding racemates were synthesized and purified to homogeneity. The influence of the position of the hydroxy group on the monolayer packing properties of these fatty acids and their phosphatidylcholines was studied by Langmuir techniques and 1,2-di-[(R)-12-hydroxy-octadec-cis-9-enyl]-sn-glycero-3-phosphocholine displayed the largest lift-off area (330 A2/molecule). This result was in line with the thermotropic phase behavior of these phospholipids, as measured by differential scanning calorimetry (DSC): the gel- to liquid-crystalline phase transition temperature (T(m))passed through a minimum of -15.1°C for 1,2-di-[(R)-12-hydroxy-octadec-cis-9-enyl]-sn-glycero-3-phosphocholine.
- Negelmann, Lars,Pisch, Sandra,Bornscheuer, Uwe,Schmid, Rolf D.
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p. 117 - 134
(2007/10/03)
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- Asymmetric Reduction of Aliphatic Short- to Long-Chain β-Keto Acids by Use of Fermenting Bakers' Yeast
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Eleven β-keto acids, ranging from 3-oxobutanoic to 3-oxooctanoic acids, were reduced with fermenting bakers' yeast to the corresponding optically active β-hydroxy acids, which were isolated as the methyl esters.In all cases, the (R)-hydroxy acids were obtained in >/=98percent ee, except for 3-oxobutanoic acid, which afforded the (S)-hydroxy acid in 86percent ee.Inhibition of fermentation was observed for 3-oxoundecanoic to 3-oxotetradecanoic acids, leading to no reduction.Lowering of the substrate concentration was found to be appreciably effective in avoiding inhibition.
- Utaka, Masanori,Watabu, Hisashi,Higashi, Hiroshi,Sakai, Takashi,Tsuboi, Sadao,Torii, Sigeru
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p. 3917 - 3921
(2007/10/02)
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- Asymmetric Reduction of 3-Oxo-octadecanoic Acid with Fermenting Baker's Yeast. An Easy Synthesis of Optically Pure (+)-(2R,3R)-Corynomycolic Acid
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Optically pure (+)-corynomycolic acid has been synthesized from methyl acetoacetate by a route including asymmetric reduction of 3-oxo-octadecanoic acid with baker's yeast as a key step.
- Utaka, Masanori,Higashi, Hiroshi,Takeda, Akira
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p. 1368 - 1369
(2007/10/02)
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