Trestatin complex which exhibited a potent inhibitory activity on various a-amylases has been isolated from the culture filtrate of Streptomyces dimorphogenes nov. sp. NR-320-OM7HB. Three major components, trestatins A, B and C, have been purified by adsorption and ionexchange chromatography.Their spectral and chemical properties suggested that trestatins were novel basic oligosaccharide homologues each characterized by the possession of a trehalose moiety at the non-reducing end of the molecule.It has been suggested that useful therapy of diabetes and obesity might be achieved by reducing the digestion of dietary starch using inhibitors of a-amylase. This could be expected to decrease hyperglycemia and hyperinsulinemia. From these viewpoints, a number of a-amylase inhibitors have been isolated from the microbial cultures.1~14) In the course of our screening program searching for a-amylase inhibitors, we discovered a novel complex, designated trestatin* in the culture filtrate of a new Streptomyces species to which we have given the name Streptomyces dimorphogenes NR-320-OM7HB. The trestatin complex contained trestatins A, B and C as the major components. They have shown a remarkable inhibitory activity against various a-amylases.The present paper describes the production by fermentation, isolation, physico-chemical characteristics and biological properties of the major components of trestatin. Their structures are reported in the subsequent paper. Mycological characteristics of the producer strain will be described elsewhere. Results and Discussions FermentationThe seed culture was prepared in a medium containing 2.0% potato starch, 2.0% glucose, 2.0 soya meal, 0.5 % yeast extract, 0.25 % NaCl, 0.005 % ZnSO4• 7H2O, 0.0005 % CuSO4 • 5H2O, 0.0005MnCl2.4H2O, 0.32% CaCO3 (pH 7.0) by shaking for 48 hours at 27°C, and transferred into a 50-liter fermentor containing 25 liters of the same medium as the seed culture. Fermentation was carried out at 27°C for 43 hours with an air flow rate of 25 liters per minute under an agitation at 300 rpm. The inhibitory activity of trestatin on porcine pancreatic a-amylase was determined by the method as described in Experimental. A typical trestatin fermentation broth (pH 6.9) had an activity of 3.1 x 104inhibi-tory unit (IU)/ml. The detailed process for the fermentation will be described elsewhere.* Parts of the present work were orally presented at 218th Scientific Meeting

Fungal strain NR6356, Fusarium merismoides Corda, was discovered as the source of the protein kinase C (PKC) inhibitor, azepinostatin.The strain was identified based on its growth on potato sucrose agar, slender conidial shape, characteristic polyphialide and production of abundant chlamydospores. Fusarium aquaeductuum Lagh. IMI 103658 and Fusarium sp. NR7222 were also found to produce the same inhibitor. After single colony isolation and mediumoptimization trials, a more than 30-fold increase in the production of azepinostatin over the original culture was achieved.Azepinostatin selectively and potently inhibited rat brain PKCwith an IC50 value of 70 nM. Other enzymes utilizing ATP, including hexokinase, were not affected. The Ki of azepinostatin for PKCwas 0.5 nM. The inhibition of PKCwas competitive with ATPand uncompetitive with histone.

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A new series of antifungal antibiotics, Ro 09-1470 and its 6 congeners were isolated from the fermentation broth of Penicillium sp. NR6564. Their structures were determined as tetrahydropyran derivatives with an alkenyl side chain on the basis of their spectroscopic and physico-chemical properties. Among these compounds, Ro 09-1470 and Ro 09-1545 possessing a glycyl or an TV-substituted glycyl ester residue had high antifungal activity. Ro 09-1469, one of the congeners, was found in the fermentation broth of several strains of Aspergillus sclerotiorum Huber.

The susceptibilities of 462 clinical anaerobic bacterial isolates to N-formimidoyl thienamycin and 16 other currently available and investigational antibiotics were determined by the agar dilution technique. N-Formimidoyl thienamycin was significantly more active than the reference antibiotics against most organisms tested, especially Bacteroides sp., including clindamycin-resistant strains. All 462 isolates were inhibited by 4 pLg of N-formimidoyl thienamycin per ml, and no resistant strains were found in the species tested. N-Formimidoyl thienamycin was less active (i.e., had a higher 50o minimal inhibitory concentration) against Fusobacterium sp. than clindailycin, SM-1652, and