Three new naturally occurring bicyclic alkaloids, jenamidines A (1), B (2) and C (3), were discovered and isolated from the culture broth of Streptomyces sp. (strain HKI0297) via the chemical screening approach. Fermentation, isolation, structure and biological activities of these three new secondary metabolites are reported. The jenamidines have an unusual octahydro-pyrido[1, 2-a]pyrimidine skeleton. Jenamidine A (1) shows antiproliferative effects against the chronic myeloid leukaemic cell line K-562. In addition, the new tricyclic sesquiterpenoid, africantriol (4) was isolated from the same strain.
A marine bacterium Ruegeria atlantica (designated as strain TUF-D) was isolated from a glass plate submerged in the coastal water. Three new chlorine containing compounds (1-3) together with penicillic acid (4) were obtained from a marine-derived fungus Aspergillusostianus strain TUF 01F313 isolated from a marine sponge at Pohnpei as antibacterial components against R. atlantica. The structures of three new antibiotics were determined based on their spectral data as 8-chloro-9-hydroxy-8, 9-deoxyasperlactone (1), 9-chloro-8-hydroxy-8, 9-deoxyasperlactone (2), and 9-chloro-8-hydroxy-8, 9-deoxyaspyrone (3). Compound 1 inhibited the growth of R. atlantica at 5μg/disc (inhibition zone: 12.7mm), while 2 and 3 were active at 25μg/disc (10.1 and 10.5mm, respectively).
A 3.5-kb DNA fragment that confers resistance to D-cycloserine (DCS) was cloned from the chromosomal DNA of a DCS-producing Streptomyces garyphalus into Streptomyces lividans by a shot-gun cloning technique. Nucleotide sequence analysis revealed the existence of four open reading frames (ORFs B, C, D, and E), together with two incomplete ORFs, A and F. By introduction of the cloned fragment into Escherichia coli, the host obtained resistance to DCS. We showed that ORF B, which consists of 903bp, is a DCS resistance gene. The hydropathy plot analysis of a protein deduced from ORF B revealed that the protein carries membrane-integral domains spanning the membrane 10 times, which suggests that the DCS-resistance determinant may be a factor associated with DCS transport.
Pradimicin A (PRM), a mannose-binding antifungal antibiotic, induced the apotosis-like cell death in Saccharomyces cerevisiae. The nuclear breakage and DNA fragmentation were observed in yeast cells by DAPI and TUNEL staining after the treatment with PRM. Accumulation of reactive oxygen species (ROS) was also detected in PRM-treated yeast cells by staining with dichlorodihydrofluorescein diacetate. PRM-induced cell death and the accumulation of ROS were prevented by pretreating the yeast cells with a radical scavenger, N-acetylcysteine. These results indicate that PRM induces the apoptosis-like cell death in yeast through the generation of ROS.
Nonomuraed sp. ATCC 39727 is the producer of the A40926 complex of lipoglycopeptide antibiotics which contain chlorine atoms in amino acids 3 and 6 of the peptide backbone. Using a classical mutagenesis and selection approach we have isolated a Nonomuraea sp. ATCC 39727 mutant strain able to direct production towards new A40926 analogues dechloro-A40926 (DDC) lacking two chlorine atoms and the two monochloro-A40926 (MDC1 and MDC2) that are not produced fermenting the wild type strain. Dechlorinated A40926 derivatives were obtained in considerable amount in a standard fermentation process and were purified and chemically characterized. The dechlorinated A40926 derivatives DDC and MDC2 showed improved antimicrobial activity against coagulase negative staphylococci strains in respect to A40926 complex. Dechlorinated derivatives of the related antibiotic teicoplanin are also reported in the literature and are generally less active than the parental products.