Puwainaphycins (PUWs) and minutissamides (MINs) are structurally analogous cyclic lipopeptides possessing cytotoxic activity. Both types of compound exhibit high structural variability, particularly in the fatty acid (FA) moiety. Although a biosynthetic gene cluster responsible for synthesis of several PUW variants has been proposed in a cyanobacterial strain, the genetic background for MINs remains unexplored. Herein, we report PUW/MIN biosynthetic gene clusters and structural variants from six cyanobacterial strains. Comparison of biosynthetic gene clusters indicates a common origin of the PUW/MIN hybrid nonribosomal peptide synthetase and polyketide synthase. Surprisingly, the biosynthetic gene clusters encode two alternative biosynthetic starter modules, and analysis of structural variants suggests that initiation by each of the starter modules results in lipopeptides of differing lengths and FA substitutions. Among additional modifications of the FA chain, chlorination of minutissamide D was explained by the presence of a putative halogenase gene in the PUW/MIN gene cluster of Anabaena minutissima strain UTEX B 1613. We detected PUW variants bearing an acetyl substitution in Symplocastrum muelleri strain NIVA-CYA 644, consistent with an O-acetyltransferase gene in its biosynthetic gene cluster. The major lipopeptide variants did not exhibit any significant antibacterial activity, and only the PUW F variant was moderately active against yeast, consistent with previously published data suggesting that PUWs/MINs interact preferentially with eukaryotic plasma membranes. IMPORTANCE Herein, we deciphered the most important biosynthetic traits of a prominent group of bioactive lipopeptides. We reveal evidence for initiation of biosynthesis by two alternative starter units hardwired directly in the same gene cluster, eventually resulting in the production of a remarkable range of lipopeptide variants. We identified several unusual tailoring genes potentially involved in modifying the fatty acid chain. Careful characterization of these biosynthetic gene clusters and their diverse products could provide important insight into lipopeptide biosynthesis in prokaryotes. Some of the variants identified exhibit cytotoxic and antifungal properties, and some are associated with a toxigenic biofilm-forming strain. The findings may prove valuable to researchers in the fields of natural product discovery and toxicology.
Prenylation is a common step in the biosynthesis of many natural products and plays an important role in increasing their structural diversity and enhancing biological activity. Muscoride A is a linear peptide alkaloid that contain two contiguous oxazoles and unusual prenyl groups that protect the amino-and carboxy-termini. Here we identified the 12.7 kb muscoride (mus) biosynthetic gene clusters from Nostoc spp. PCC 7906 and UHCC 0398. The mus biosynthetic gene clusters encode enzymes for the heterocyclization, oxidation, and prenylation of the MusE precursor protein. The mus biosynthetic gene clusters encode two copies of the cyanobactin prenyltransferase, MusF1 and MusF2. The predicted tetrapeptide substrate of MusF1 and MusF2 was synthesized through a novel tandem cyclization route in only eight steps. Biochemical assays demonstrated that MusF1 acts on the carboxy-terminus while MusF2 acts on the amino-terminus of the tetrapeptide substrate. We show that the MusF2 enzyme catalyzes the reverse or forward prenylation of amino-termini from Nostoc spp. PCC 7906 and UHCC 0398, respectively. This finding expands the regiospecific chemical functionality of cyanobactin prenyltransferases and the chemical diversity of the cyanobactin family of natural products to include bis-prenylated polyoxazole linear peptides.
Aromatic prenylation is an important step in the biosynthesis of many natural products and leads to an astonishing diversity of chemical structures. Cyanobactin pathways frequently encode aromatic prenyltransferases that catalyze the prenylation of these macrocyclic and linear peptides. Here we characterized the anacyclamide (acy) biosynthetic gene cluster from Anabaena sp. UHCC-0232. Partial reconstitution of the anacyclamide pathway, heterologous expression and in vitro biochemical characterization of the enzyme demonstrate that the AcyF enzyme encoded in this biosynthetic gene cluster is a Trp N-prenyltransferase. Bioinformatic analysis suggests the monophyletic origin and rapid diversification of the cyanobactin prenyltransferase enzymes and the multiple origins of N-1 Trp prenylation in prenylated natural products. The AcyF enzyme displayed high flexibility towards a range of Trp-containing substrates and represents an interesting new tool for biocatalytic applications.
ObjectivesTo investigate the role of socioeconomic status and psychological stress to potential associations between confidence in the future and a wide range of health-related behaviours.DesignWeb-based cross-sectional study including an ‘Electronic Health Check’ at the Finnish Happiness-Flourishing Study website linked to a TV programme on happiness and depression.SettingThe Finnish population with access to the internet.Participants101 257 Finns aged 18 and above (21 365 men; 79 892 women). Participants who were under the age of 18 and who did not provide information about their gender were excluded.Primary outcome measuresAs planned, we assessed smoking, weekly alcohol consumption and binge drinking, daily intake of fruits and vegetables and regular exercise.ResultsCompared with participants with low confidence in the future, those with high confidence were less likely to be daily smokers (men OR 0.58, 95% CI 0.52 to 0.65; women 0.57, 95% CI 0.53 to 0.61) and binge drinkers (men 0.57; 0.52 to 0.63; women 0.54; 0.50 to 0.57). Participants with high confidence in the future were more likely to exercise regularly (men OR 2.82, 95% CI 2.55 to 3.13; women 2.57, 95% CI 2.44 to 2.71) and consume vegetables (men OR 2.48, 95% CI 2.25 to 2.74; women 2.13, 95% CI 2.03 to 2.24) and fruits (men OR 2.09, 95% CI 1.86 to 2.35; women 1.83, 95% CI 1.74 to 1.93) daily. Adjustment for current psychological distress and satisfaction for income attenuated the results.ConclusionsHaving confidence in the future is strongly associated with a healthy lifestyle, as assessed by a healthy diet, physical exercise and substance abuse. Health-related interventions may benefit from tailoring interventions according to the target population's level of confidence in the future as well as their level of psychological distress.
A series of resol-type phenol-formaldehyde resins was investigated by infrared spectroscopy and differential scanning calorimetry. The molar ratio of phenol to formaldehyde was determined from the absorbance ratio D lolo/D 1610 Differences between the reactivities of resins were confirmed by the molar phenol to formaldehyde ratio, heat of reaction and gelation time. ZUSAMMENFASSUNG:Eine Reihe von Phenol/Formaldehyd-Resol-Harzen wurde mit Hilfe der IR-Spektroskopie und der DSC-Methode (Differential Scanning Calorimetry) untersucht. Das Mol-Verhaltnis zwischen Phenol und Formaldehyd wurde auf der Basis des Absorptionsverhaltnisses D bestimmt. Die Unterschiede zwischen der Reaktivitat von verschiedenen Harzen wurden mit Hilfe von molaren Phenol-Formaldehyd-Verhaltnissen, der Reaktionswarme und der Gelierungszeit festgestellt.
The specific heat, Cp, was determined by DSC on a series of resol-type phenol formaldehyde resins with varying phenol formaldehyde molar ratio. The extrapolated Cp values at 25°C vary between 1.181-1.206kJ.kg-'K-' and the dCp/dT ratio was found to be 0.0042kJ.kg-' K-' in the temperature range of 70-125°C.
SamnuuTyThe purpose of this study is to elucidate the background of drug-taking among three different age groups (17, 15 and I4years old) of schoolchildren in Helsinki. The method used was a questionnaire. 25% of all the schoolchildren had taken drugs, hashish being used most frequently. The social background of drug-takers and non-takers did not differ greatly. On the other hand, the emotional stability of the home was of importance. The drug-takers did worse at school, they were more extrovert, more impulsive and they had more friends. They were also more rebellious and more alienated. In neuroticism controversial results were found. The most important reason leading to drug-taking reported by the schoolchildren was curiosity. Amongyouth at large, different problems and social pressures were also thought to lead to drug-taking.
Applications of thermoanalytical methods for the study of resinification, curing and thermal degradation of phenolic and epoxy resins are reviewed. The curing properties of PF resins and various epoxy systems~ determined by thermal methods~ are illustrated.Phenolic and epoxy resins are the most common thermosets utilized by the plastics-processing industry. In the cured state they are infusible, insoluble, covalently-cross-linked, thermally stable network polymer structures. The formation of this network structure is responsible for the desirable physical properties which are typical of thermosetting resins over a broad temperature range.Owing to their intractable nature, the thermosetting resins are difficult to study by chemical means. Numerous investigations have shown that thermoanalytical techniques offer valuable tools for the study of the formation, the curing characteristics and the thermal degradation of these resins.The purpose of this paper is to survey the thermoanalytical methods such as differential thermal analysis (DTA), differential scanning calorimetry (DSC), thermogravimetry (TG) and thermomechanical methods, which have been successfully applied to the elucidation of the thermal characteristics of phenolic and epoxy resins. Phenol-formaldehyde resinsWhen phenol reacts with formaldehyde four major reactions occur: a) addition to give methylol phenols; b) condensation of a methylol phenol and a phenol to give a methylene bridge; c) condensation of two methylol groups to give an ether bridge; d) decomposition of ether bridges to methylene bridges and formaldehyde.The reaction is catalyzed by acids or by bases to give novolacs or resols respectively. The nature of the product is dependent on the type of catalyst and the molar ratio of the reactants. Addition and condensation are exothermic reactions, and therefore thermoanalytical methods are particularly suited for elucidation
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