A group of cyclic peptides consisting of 8 amino acid residues, named argyrins A to H, were isolated from the culture broth of strains of the myxobacterium Archangium gephyra. Argyrin B was found to be a potent inhibitor of T cell independent antibody formation by murine B cells and strongly inhibited the two way murine mixed lymphocyte reaction. All argyrins had slight antibiotic activity, especially against Pseudomonas sp., and inhibited growth of mammalian cell cultures. The growth inhibition was often incomplete and varied highly with different cell lines.
In the search for new naturally occurring anti-angiogenic compounds, we found that a culture broth of an unidentified fungal strain B90911 exerted inhibitory activity on capillarylike tube formation of human umbilical vein endothelial cells (HUVEC) in vitro. Four active compounds were isolated by bioassay-guided separation and their structures were identified to be sulochrin (1), methyl asterric acid (2), and two new asterric acid derivatives, 3-chloroasterric acid (3), and 3, 5-dichloroasterric acid (4) by spectroscopic analyses. These compounds significantly inhibited the VEGF-induced tube formation of HUVEC, suggesting that asterric derivatives could be useful for further study as anti-angiogenic agents.
Seven new peptaibols, atroviridins A-C composed of 20 residue amino acids and neoatroviridins A-D with 18 residues, were isolated from the culture broth of fungal strain F80317. The strain F80317 was identified as Trichoderma atroviride from its morphological and cultural characteristics. These compounds showed antimicrobial activity against Grampositive bacteria and phytopathogenic fungi, and exhibited significant cytotoxicity to human cancer cell lines in vitro. Atroviridins showed significant membrane-perturbing activity responsible to their antibiotic action.
New lipopeptide antibiotics, colourless arylomycins A series and yellow arylomycins B series were detected in the culture filtrate and mycelium extracts of Streptomyces sp. Tü 6075 by HPLC-diode-array and HPLC-electrospray-mass-spectrometry screening. Arylomycins are a family of lipohexapeptide antibiotics, which represent the first examples of biaryl-bridged lipopeptides. They show antibiotic activities against Gram-positive bacteria.
The structures of new lipopeptide antibiotics, arylomycins A and B, were elucidated by a combination of ESI-FTICR-mass spectrometry, NMR spectroscopy, EDMAN sequencing, and fatty acid and chiral amino acid analyses. The colourless arylomycins A share the peptide sequence of D-N-methylseryl2(D-MeSer2)-D-alanyl3-glycyl4-N-methyl-4-hydroxyphenylglycyl5-(MeHpg5)-L-alanyl6-tyrosine7 cyclised by a [3, 3]biaryl bond between MeHpg5 and Tyr7. The yellow arylomycins B differ from arylomycins A by nitro substitution of Tyr7. The N-termini of arylomycins A and B are acylated with saturated C11-C15 fatty acids (fa1) comprising n, iso, and anteiso isomers. Arylomycins A and B represent the first examples of biaryl-bridged lipopeptides.
The biosynthetic pathway leading to the cyclitol moiety of pyralomicin 1a (1) in Nonomuraea spiralis MI178-34F18 has been studied using a series of 2H-labeled potential precursors. The results demonstrate that 2-epi-5-epi-valiolone (7), a common precursor for acarbose (4) and validamycin A (5) biosynthesis, is an immediate precursor of pyralomicin 1a. 5-epi-Valiolone (8) was also incorporated into 1, albeit less efficiently than 7. Other potential intermediates, such as valiolone (9), valienone (10), valienol (11), 1-epi-valienol (12), 5-epi-valiolol (13), and 1-epi-5-epi-valiolol (14) were not incorporated into pyralomicin 1a. To explain this surprising observation, it is proposed that either 2-epi-5-epi-valiolone (7) is specifically activated (e.g., to its phosphate) and that the further transformations take place on activated intermediates (which can not be generated directly from their unactivated counterparts), or that the transformation of 7 into 1 involves a substrate-channeling mechanism in which enzyme-bound intermediates are directly transferred from one enzyme active site to the next in a multi-enzyme complex.
Three inhibitors of cell adhesion based on LFA-1/ICAM-1 were isolated from the cultured broth of the fungal strain Mycotypha sp. UMF-006. These compounds were identified by spectroscopy to be cytochalasin E (1), 5, 6-dehydro-7-hydroxy derivative of cytochalasin E (2) and Δ6, 12-isomer of 2 (3). All these components inhibited adhesion of HL-60 cells to CHO-ICAM-1 cells at IC50 values of 30μg/ml for 1, 75μg/ml for 2, and 90μg/ml for 3.