Uncovering biosynthetic relationships between antifungal nonadrides and octadrides.

12/15-Lipoxygenase gene disruption and Vitamin E administration diminish atherosclerosis and oxidative stress in apolipoprotein E deficient mice through a final common pathway

Bioactive metabolites from marine microorganisms

Kallmann syndrome (KS) is a congenital disorder characterized by idiopathic hypogonadotropic hypogonadism and olfactory dysfunction. KS is linked to variants in >34 genes, which are scattered across the human genome and show disparate biological functions. Although the genetic basis of KS is well studied, the mechanisms by which disruptions of these diverse genes cause the same outcome of KS are not fully understood. Here we show that disruptions of KS-linked genes affect the same biological processes, indicating convergent molecular mechanisms underlying KS. We carried out machine learning-based predictions and found that KS-linked mutations in heparan sulfate 6-O-sulfotransferase 1 (HS6ST1) are likely loss-of-function mutations. We next disrupted Hs6st1 and another KS-linked gene, fibroblast growth factor receptor 1 (Fgfr1), in mouse neuronal cells and measured transcriptome changes using RNA sequencing. We found that disruptions of Hs6st1 and Fgfr1 altered genes in the same biological processes, including the upregulation of genes in extracellular pathways and the downregulation of genes in chromatin pathways. Moreover, we performed genomics and bioinformatics analyses and found that Hs6st1 and Fgfr1 regulate gene transcription likely via the transcription factor Sox9/Sox10 and the chromatin regulator Chd7, which are also associated with KS. Together, our results demonstrate how different KS-linked genes work coordinately in a convergent signaling pathway to regulate the same biological processes, thus providing new insights into KS.

During the isolation of human parathyroid hormone there is an extensive loss of immuno-assayble hormone over the successive extraction steps, due in part to the presence of fragments that are soluble in 4% trichloroacetic acid. These fragments are derived from both the amino- and carboxyl-terminal regions of the hormone. The hormonal fractions precipitated with trichloroacetic acid were further purified by gel filtration and ion-exchange chromatography. At the final ion-exchange purification step, some preparations of the hormone eluted in multiple fractions. When the various components were characterized separately by immunoassay, amino acid composition, enzymic cleavage and partial sequence analysis, they were found to be closely comparable, although the most acidic fraction contained a blocked terminal amino group. Extraction of a number of batches of tissue permitted revision of the amino acid composition of human parathyroid hormone. Biosynthetic studies with labelled amino acids confirmed the absence of tyrosine and the presence of phenylalanine and threonine and localized these residues to definite regions of the molecule.

Medicinal plants are rich sources for treating various diseases due their bioactive secondary metabolites. Fenugreek (Trigonella foenum-graecum) is one of the medicinal plants traditionally used in human nutrition and medicine which contains an active substance, called diosgenin, with anticancer properties. Biosynthesis of this important anticancer compound in fenugreek can be enhanced using eliciting agents which involves in manipulation of metabolite and biochemical pathways stimulating defense responses. Methyl jasmonate elicitor was used to increase diosgenin biosynthesis in fenugreek plants. However, the molecular mechanism and gene expression profiles underlying diosgening accumulation remain unexplored. In the current study we performed an extensive analysis of publicly available RNA-sequencing datasets to elucidate the biosynthesis and expression profile of fenugreek plants treated with methyl jasmonate. For this purpose, seven read datasets of methyl jasmonate treated plants were obtained that were covering several post-treatment time points (6–120 h). Transcriptomics analysis revealed upregulation of several key genes involved in diosgenein biosynthetic pathway including Squalene synthase (SQS) as the first committed step in diosgenin biosynthesis as well as Squalene Epoxidase (SEP) and Cycloartenol Synthase (CAS) upon methyl jasmonate application. Bioinformatics analysis, including gene ontology enrichment and pathway analysis, further supported the involvement of these genes in diosgenin biosynthesis. The bioinformatics analysis led to a comprehensive validation, with expression profiling across three different fenugreek populations treated with the same methyl jasmonate application. Initially, key genes like SQS, SEP, and CAS showed upregulation, followed by later upregulation of Δ24, suggesting dynamic pathway regulation. Real-time PCR confirmed consistent upregulation of SQS and SEP, peaking at 72 h. Additionally, candidate genes Δ24 and SMT1 highlighted roles in directing metabolic flux towards diosgenin biosynthesis. This integrated approach validates the bioinformatics findings and elucidates fenugreek’s molecular response to methyl jasmonate elicitation, offering insights for enhancing diosgenin yield. The assembled transcripts and gene expression profiles are deposited in the Zenodo open repository at https://doi.org/10.5281/zenodo.8155183.

Chapter 5 - Antioxidant, anti-inflammatory and anticancer potential of natural bioactive compounds from seaweeds

Increased fucosylation has a pivotal role in multidrug resistance of breast cancer cells through miR-224-3p targeting FUT4

Endophytic fungi have currently been acknowledged as the most promising source of bioactive compounds for drug discovery, and considerable progress has been made in exploring their diversity, species richness, and bioprospecting. Fungal endophytes from unique environmental settings offer a pool of potentially useful medicinal entities. Owing to the constant stresses imposed on macroalgae by marine environments, it is believed that algae and their associated endophytic symbionts represent a good source of structurally diverse bioactive secondary metabolites. Despite the proven significance of active metabolites of algal endophytes, little have been exploited. This review highlights the latest discoveries in algicolous endophytic research, with particular focus on the bioactive metabolites from algal endophytes. Compounds are classified according to their reported biological activities, like anticancer, antibacterial, antifungal, and antioxidant properties. Present experimental evidence suggests that a majority of the bioactive metabolites were reported from Phaeophyceae followed by Rhodophyceae and Chlorophyceae. An intensive search for newer and more effective bioactive metabolites has generated a treasure trove of publications, and this review partially covers the literature published up to 2016.

Herbivorous mammal dung supports a large variety of fimicolous fungi and the number of new genera and species is constantly increasing. Dung is a complex ecosystem and to win the struggle for life, these fungi produce a plethora of bioactive secondary metabolites to compete with other organisms. Fimicolous fungi and their bioactive metabolites are mostly evaluated for a possible use in medicine. Very little information is available about their possible exploitation in agriculture against plant pathogens. Three fimicolous isolates of Cleistothelebolus nipigonensis, Neogymnomyces virgineus and Rodentomyces reticulatus, collected from dung of different herbivorous were investigated. Only the organic extracts of Solid State Fermentation (SSF) cultures of C. nipigonensis and N. virgineus grown on rye flour showed strong antifungal activity against fungal pathogens of some important crops. The purification of the organic extracts allowed us to obtain different fractions and the isolation of some pure metabolites and their preliminary chemical and biological characterization are reported in this manuscript.

Antagonistic bacteria have been repeatedly shown to be promising microorganisms for the biological control of sedentary and migratory endoparasitic nematodes. Depending on the bacteria involved, the mechanisms of action include: obligate parasitism, reduction in penetration, growth inhibition due to competition for nutrients and antibiosis associated with bioactive metabolites. In the present studies, the mode of action of the antagonist bacteria Bacillus firmus, isolated from a bionematicide, was evaluated. Significant rates of paralysis and mortality were detected after incubation of three nematode species in low concentrations of the pure culture filtrates following removal of the bacterial cells. The same culture filtrates also significantly reduced hatching of Meloidogyne incognita. Pure bacterial cell suspensions added to sand also reduced survival of R. similis in bioassays by 41% over the controls. The mode-of-action responsible for nematode paralysis and mortality was therefore demonstrated to be closely associated with the production of bioactive compounds secondary metabolites by the bacteria.

Structural and biosynthetic studies on eremophilenols related to the phytoalexin capsidiol, produced by Botrytis cinerea

Engineered biosynthesis of novel polyketides: evidence for temporal, but not regiospecific, control of cyclization of an aromatic polyketide precursor

Structural and biosynthetic studies on linkage region between poly(galactosylglycerol phosphate) and peptidoglycan in Bacillus coagulans

21] Purification of rhodopsin on agarose

A 7‐year‐old English girl was found to have a lobar pneumonia with a marked haemolytic anaemia. Routine electrophoresis revealed no abnormal haemoglobin but, as anticipated, an unstable haemoglobin fraction readily formed in haemolysates on routine in vitro instability tests. From the subsequent structural and biosynthetic studies it was concluded that the propositus' red cells contained, in addition to Hbs A, A2 and F, two unstable haemoglobins with abnormalities in the primary structure of their non α‐chains: Hb Sydney and Hb Coventry. The first has an amino acid substitution Val→Ala at position β67 (E11), while the other, Hb Coventry, is a new variant with a non α‐chain which resembles the βA‐chain except that the leucine residue at position β141(H19) is deleted. This suggests that, instead of the normal complement of two β‐chain genes, the propositus' genome has three, i.e. βA‐, βSydney‐ and βCoventry‐chain genes. Evidence is presented from which it can be concluded that the non α‐chain of Hb Coventry, whilst being structurally a β‐chain variant is, in fact, a βδ fusion chain variant with 140β‐ and 5δ‐chain residues. The oxygen dissociation curve of the propositus showed a reduced affinity at the upper part of the curve, a feature which she shared with a straightforward heterozygote for Hb Sydney, and a slight shift to the left in the lower part, a feature which she shared with her father who possessed Hb Coventry.