Caerulomycin A—An Antifungal Compound Isolated from Marine Actinomycetes

Actinomycetes have been prolific sources of novel secondary metabolites with a range of biological activities that may ultimately find application as therapeutic compounds. Hence several drug discovery companies are engaged in isolation of novel bioactive metabolites from these microbial sources. Antibiotics form the major class of such bioactive metabolites and have been widely used for treating infectious diseases. One of the most critical problems in clinical practice is the increase of prevalence of drug resistant strains, especially azole resistance among fungi. Due to this, there is a constant need for development of new antifungal antibiotics having novel scaffolds and/or mechanism of action. In our in-house screening program in the quest of novel and superior antifungal compounds, an actinomycetes strain PM0525875 was isolated from a marine invertebrate. The extracts of this microbe showed potent in-vitro antifungal activity against drug resistant fungal strains. The antifungal active peak from the extract obtained by shake flask fermentation was identified by chromatographic and other analytical techniques during bioactivity guided isolation. Later the fermentation conditions were optimized in 30 L fermentor for the production of sufficient amount antifungal compound for complete structural characterization. Consequently the fermented broth extract was subjected to bioactivity-guided fractionation, to isolate the active principle using different preparative chromatographic techniques followed by its characterization. The active principle was characterized to be Caerulomycin A. Minimum inhibitory concentration (MIC) of the compound was found in the range of 0.39 - 1.56 μg/ml against pathogenic fungal test strains. The phylogenetic analysis of producer strain using 16S rRNA sequence showed closest match with Actinoalloateichus cyanogriseus. Herewith we report the isolation of Caerulomycin A from marine invertebrate-associated Actinoalloteichus sp. using optimized medium and fermentation conditions.

Synthesis and Characterization of a Red Clay Based New Composite Ceramic Material

In this study, a new composite ceramic material using a red clay matrix with different amount of clinker from the cement industry has been developed. The aim is to valorize some natural resources such as red clay and sub-products from the cement industry as clinker in order to develop new materials for industrial and/or catalytic uses. Raw materials were grounded in order to reduce the particle size and obtain a homogeneous slip. The samples were mixed and compressed into pellets and undergo a heat treatment up to 1100℃. Geotechnical characterization has been carried out. Firing proprieties (shrinkage, water absorption, and mechanical resistance to the inflection) were measured. The composition of the ceramic material was investigated by X-ray diffraction, XRF, SEM and EDS methods. The incorporation of clinker in the ceramic composite material up to 50 wt% exhibits good behaviors (physical and mechanical proprieties) and can be used as a ceramic product.

Spontaneous Polymerization of An Amino Acid Based Amphiphile at Air/water Interface Investigated by ESI-MS and Transmission IR Spectrometry

Self-assemblies of amphiphilic molecules are proposed to play a ubiquitous role at the early stages of evolution in the formation of primitive biopolymers. [1] As regard to the significance of N-phosphoryl amino acids as a model for the co-evolution of protein and nucleic acids at the prebiotic stage, [2] amphiphilic N-phosphoryl amino acids with two hydrophobic tails were synthesized. [3]……

THE DIFFERENTIATION BETWEEN N-PHOSPHORYL HOMO-SERINE AND SERINE

Chemically, N-phosphoryl homo-serine was much more stable than the homologous compound phosphorylated serine. The latter was very reactive to undergo N -->O migration, formation of peptide and cyclophosphoroamidate but not the former when they were warmed in alcohol or chloroform at 40 degreesC. For the N-phospho-homo-serine, only a small extent of ester exchange occurred on the phosphorus. A second type of penta-coordinate phosphorus intermediate was proposed.

Orientation of the peptide formation of N-phosphoryl amino acids in solution

The peptide formation of N-phosphoryl aminoacids with amino acids proceeds in aqueous solution withoutany coupling reagents. After being separated in sephadex gelcolumn, the phosphoryl dipeptides were analyzed by theelectrospray ionization tandem mass spectrometry (ESIMS/MS). The result demonstrates that phosphoryl dipeptideswere datected in all the reaction systems. It is found tkat theformation of N-phosphoryl dipeptides is oriented: theN-terminal amino acid residues of the N-phosphoryl dipep-tides are from N-phosphoryl amino acids, and the peptideelongation happened at the C-terminal. Only adipeptide, noβ-dipeptide, is formed in the N-phosphoryl dipeptides,showing that α-carboxylic group is activated selectively byN-pbosphorylation. Theoretical calculation shows that thepeptide formation of N-phosphoryl amino acids might hap-pen through a pentu-coordinate carboxylic-phosphoric in-termediate in solution. These results might give some clues tothe stlidy on the origin of proteins and protein

Mechanism of intramolecular mixed anhydride formation as intermediates in the reactions of N-phosphorylamino-acids──An MNDO research

N-phosphoryl-α-amino acids can react to form esters, peptides, phosphoryl ester-exchanged products and phosphoryl group migration products under mild conditions, which are very important in researches on arohebiont. It has been proposed that intramolecular mixed carboxylic-phosphoric anhydrides (IMCPAs) might be the common intermediates of the reactions, which are difficult to be experimentally observed because of their high activity. In this note, it has been revealed, by means of MNDO, that the IMCPAs are situated at the relatively minimal points of the potential surface and can form in a non-synchronous concerted reaction pathway that passes through a transition state with a hydrogen-bond-bridge structure. The results give a successful explanation to the structure and formation of IMCPAs and their ability to promote the various reactions mentioned above.

Novel ions of quaternary ammonium halides in FDMS

Field desorption mass spectrometry exhibited novel ions [ Y-n H+n R ]+and [ Y-nH+nX]+as well as cluster ions [nY+(n-1)X-mH+mR]+and [nY+( n-1)X-mH+mX]+(n,m=0-3; X and Y represent the cation and anion moieties of quaternary ammonium halides),whose formation mechanism was discussed.

LC-MS analysis of the formed peptides from N-(O,O-diiso-propyl)phosphoryl aspartic acid

LC-ESI-MS method was used to analyze the formed di and tri-peptide in the reaction system of N-(O, O-diisopropyl) phosphoryl aspartic acid and adenosine. Cluster ions of the peptides were given in the ESI-MS. The structures of these small peptides were confirmed by LC-MS-MS analysis. Compared with the traditional HPLC-UV detection, this method showed good sensitivity and selectivity for peptide in the presence of compounds with strong UV absorption, such as nucleoside and nucleotide.