Masaaki Kizuka

A-102395, a New Inhibitor of Bacterial Translocase I, Produced by Amycolatopsis sp. SANK 60206

Bacterial phospho-N-acetylmuramyl-pentapeptide translocase (translocase I: EC 2.7.8.13) is a key enzyme in peptidoglycan biosynthesis, and a known target of antibiotics. Here we report a new nucleoside inhibitor for translocase I, A-102395, isolated from the culture broth of the strain Amycolatopsis sp. SANK 60206. A-102395 is a new derivative of capuramycin that has the benzene with a uniquely substituted chain instead of an aminocaprolactam. A-102395 is a potent inhibitor of bacterial translocase I with IC50 value of 11 nM, but possesses no antimicrobial activity against various strains tested.

A-90289 A and B, new inhibitors of bacterial translocase I, produced by Streptomyces sp. SANK 60405

During the course of screening for translocase I inhibitors, the new liposidomycin-related compounds, A-90289 A and B, were isolated from a culture broth of Streptomyces sp. SANK 60405. The structural elucidations were carried out by NMR and high-resolution mass spectral analyses, and they were classified as members of the liponucleoside antibiotics group with a sulfate group at the C-2′ position. A-90289 A and B inhibited bacterial translocase I with IC50 values of 36.5 ng ml−1 and 33.8 ng ml−1, respectively.

A-94964, a novel inhibitor of bacterial translocase I, produced by Streptomyces sp. SANK 60404. I. Taxonomy, isolation and biological activity.

Bacterial phospho-N-acetylmuramyl-pentapeptide translocase (translocase I: EC 2.7.8.13) is a key enzyme in peptidoglycan biosynthesis, and a known target of antibiotics. Here we report a novel nucleoside inhibitor against translocase I, A-94964, isolated from the culture broth of the strain Streptomyces sp. SANK 60404. A-94964 inhibited bacterial translocase I with IC50 value of 1.1 μg/ml, and showed antimicrobial activities against Staphylococcus aureus and Enterococcus faecalis with MIC of 100 and 50 μg/ml, respectively. A-94964 did not show cytotoxicity against mammalian cell lines.

Studies on novel HIF activators, A-503451s.I. Producing organism, fermentation, isolation and structural elucidation

In the course of our screening for activators of hypoxia-inducible factor (HIF), A-503451 A and virantmycin were isolated from the cultured broth of an actinomycete strain, Streptomyces sp. SANK 60101. From the same culture, the non-active homologs A-503451 B and D were also isolated. A-503451 A and virantmycin activated HIF-dependent reporter gene expression with EC50 values of 8 and 17 ng ml−1, respectively. They are highly potent activators of HIF and thus may be therapeutically useful for erythropoiesis and neural cell protection.