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In the course of screening for new bioactive compounds,a newantibiotic has been isolated from a fungal strain Aspergillus flavipes TC 1446 and was designated TMC-169. Spectroscopic analyses revealed that TMC-169 was a new analog of the aspochalasin group, represented by aspochalasins A~GX~3) and phomacin C4). This paper briefly describes the taxonomy, isolation, physico-chemical properties, structure elucidation and biological activity of TMC-169. The producing strain TCI446, a soil isolate, was S. Suzuki, T. Uchida & S. Komatsubara: TMC-1 A, B, C and D, new antibiotics of the manumycin group produced by Streptomyces sp. Taxonomy, production, isolation, physico-chemical properties, structure elucidation and biological properties.

Newdipeptidyl peptidase IV inhibitors, TMC-2A,-2B, and -2C, were isolated from the fermentation broth of Aspergillus oryzae A374. On the basis of chemical, spectroscopic and X-ray crystallographic analyses, their structures were established to be peptide-like compounds composed of three moieties, L-tryptophan, mono-or dihydroxy-L-leucine and highly substituted isoquinoline.In our search for dipeptidyl peptidase IV (DPIV) inhibitors from microbial metabolites, we discovered three novel inhibitors, TMC-2A (1), -2B (2) and -2C (3) (Fig. 1) produced by Aspergillus oryzae A374. Our previous paper1} has described the taxonomy, the fermentation, and the biochemical properties of 1, 2 and 3. This paper deals with the isolation, physico-chemical properties and structural determination of these inhibitors.

TMC-2A(1),-2B (2) and-2C (3), novel dipeptidyl peptidase IV (DPIV) inhibitors, were isolated from the fermentation broth of Aspergillus oryzae A374. TMC-2A,-2B and-2C inhibited rat kidney DPIV with IC50 value of 8.1 /jm, 17/jm, and 20^m, respectively, as well as human DPIV prepared from mononuclear cells and adenocarcinoma cells. TMC-2compounds inhibited only DPIV among the proteases tested, indicating their high selectivity for DPIV. The kinetic analyses revealed that TMC-2A was an uncompetitive inhibitor. Taxonomyand fermentation of the producing strain are also described. Dipeptidyl peptidase IV (DPIV, EC 3.4.14.5) is a serine protease which cleaves X-proline dipeptides from the NH2 termini of peptides1>2). This enzyme is a membrane-bound glycoprotein and widely distributed on a variety of cells and tissues. The highest activity is found in the kidney and the intestinal brush-border membrane3 '4). Recently, DPIV has been identified as CD26, a surface differentiation marker in the transduction of mitogenic signals in thyniocytes and T Iymphocytes5'6). DPIV/

A new endothelin converting enzyme (ECE) inhibitor, TMC-66 was isolated from the fermentation broth of Streptomyces sp. A5008. The structure of TMC-66was elucidated by spectroscopic analyses to be a new memberof benzo[a]naphthacenequinone class of antibiotics. TMC-66had a highly selective inhibitory activity for ECEwith an IC50 value of 2.9 jum. Taxonomy of the producing strain is also described.