A newdifferentiation screening system employing a humanneuroblastoma cell line. NB-1, was used to isolate staurosporine as an inducer obtained from the culture broth of Streptomyces actuosus. Staurosporine at a concentration of 20nM induced elongation of neurites and cell enlargement one hour after treatment of NB-1. In addition, the agent had a cytotoxic effect against NB-1 at a concentration of more than 0.21 /zm.
Penicillium brevicompactum ATCC16024 produced 1.7 g/1 of mycophenolic acid (MPA) in the culture medium.Various drug-resistant mutants, showingresistance to such as polyene antibiotics, chemotherapeutic agents, redox indicator and surfactants, were derived from the fungus. Most of the mutants produced 2.0~2.5 g/1 of MPA.A cloflbrate and dodecyltrimethylammonium chloride double resistant mutant, No. 4-23-1 1, produced 4.7 g/1 of MPA. A monofluoroacetic acid resistant strain, No. 5-1, derived from No. 4-23-ll produced 5.3g/1 of MPA. A methionine auxotroph, M-l, derived from ATCC16024, produced 4.0g/1 of MPA. A glutamate auxotroph, G-42, derived from strain No. 4-23-1 1 produced 5.8 g/1 of MPA. G-42 grew on L-aspartate instead of L-glutamate, and showed one-third the pyruvate carboxylase activity of the parent. Another glutamate auxotroph, G-78, did not produce MPAbut accumulated 1.5 g/1 of acetate in the culture medium,and showedone-fifth the citrate synthase activity of the parent strain. Mycophenolic acid (MPA) is a metabolite produced by several species of Penicillium, including P. brevicompactum and P. stoloniferum.l) MPA has been reported to exhibit biological activity against fungi, bacteria, tumors, viruses and psoriasis.1* Abiosynthetic pathway for MPAwas proposed by Birch.2) Both the phenolic nucleus and the sevenmemberedsidechain of MPAare formed from acetate units. Breeding of a MPAproducer was reported by Queener et al. with polyene antibiotic-resistant mutants of P. stoloniferum.3) But no other breeding study has been reported. This paper deals with production of MPA by various drug-resistant and methionine or glutamate auxotrophic mutants of P. brevicompactum. MATERIALS AND METHODS Microbial strain and culture medium. Penicillium brevi-compactum ATCC16024 was used as the original strain. Medium 1 was composed of 10g of glucose, 2g of
The culture broth of Streptomyces No. 701, isolated from a soil sample, inhibited de novo starch synthesis. Cotyledon disc bioassay1~3) showed that it also inhibited oxygen evolution from photosynthesis. The active compound, called No. 701, was isolated and identified as laidlomycin.4~6) This paper concerns the isolation, identification,. and inhibition of photosynthesis of this compound.
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