The strobilurins - New antifungal antibiotics from the basidiomycete Strobilurus tenacellus.

Abstract

The strobilurins are two antifungal antibiotics which were isolated from the mycelium of Strobilurus tenacellus strain No. 21602. The strobilurins A and B are highly active against yeasts and filamentous fungi. In vitro antitumor activity was tested using cells of the ascitic form of EHRLICH carcinoma.The strobilurins strongly inhibited the incorporation of radioactive leucine, uridine, and thymidine into the acid-insoluble fraction of cells (protein, RNA, and DNA). The molecular formulas as determined by high resolution mass spectrometry are C,6H,603 for strobilurin A and C17H19ClO4 for strobilurin B. The basidiomyceteStrobilurus tenacellus is a small agaric growing on decaying cones of Purus silverstris.Cultures of this species growing on agar plates or in submerged culture show marked antifungal activity. From the mycelium of Strobilurus tenacellus strain No. 21602 we have isolated two antibiotics which have been named strobilurins A and B. In the following paper we wish to report the fermentative production, the isolation, and the chemical and biological characterization of the strobilurins. The determination of the structure will be subject of a second publication. FermentationStrobilurus tenacellus 21602 was maintained on agar slants of a yeast extract-malt extract (YM) medium (4g yeast extract, 4 g glucose, 10 g malt extract per liter). For submerged cultivation a 150 ml of YM medium was inoculated with mycelium from one agar slant and incubated for 5 days on a rotary shaker at 22°C and 120 rpm. This culture was used to inoculate 10 liters of the same medium in a New Brunswick FS 314 fermentation apparatus. One ml of polyol antifoam was added initially, and the mycelia were grown at 22°C with mechanical stirring (150 rpm), and an aeration rate of 2 liters air/min. IsolationThe mycelia from a 10-liter culture grown for 4 days were collected on a Buchner funnel, and washed several times with water. The cells (wet weight 210 g) were extracted first with 600 ml of methanolacetone (2: 1), and then with 700 ml of methanol. The combined extracts were evaporated and the antibiotics were extracted with 100 ml of chloroform from the residue. The chloroform was dried over anhydrous Na2SO4 and evaporated yielding 3.1 g of a dark brown oil. The crude extract was

Antibiotics from basidiomycetes. IX. Oudemansin, an antifungal antibiotic from Oudemansiella mucida (Schrader ex Fr.) hoehnel (Agaricales).

“…In order to determine the relative configuration of this antibiotic an X-ray analysis was performed. Crystals of 2 are monoclinic, space group P21, with cell dimensions a=10.101 (4), b=9.596 (4), c=8.789 (4) A, f=105.40 (2). Because of the small linear absorption factor [u=6.81 cm -1 (Cu km)] and the small …”

Isolation and Characterization of Two Verrucarins from Myrothecium roridum

“…The antimicrobial spectra were determined in an agar plate diffusion test as described previously (Anke et al, 1977). Cytotoxic effects were determined according to Zapf et al (1995) with the following modifications: MCF-7 cells (DSMZ ACC 115, human breast adenocarcinoma), MDA-MB-231 cells (ATCC HTB 26, human breast adenocarcinoma) and HEP-G2 cells (DSMZ ACC 180, human hepatocellular carcinoma) were grown in D-MEM medium (GIBCO, BRL) supplemented with 10% fetal calf serum (FCS) (GIBCO, BRL), 65 μg/ml penicillin G and 100 μg/ml streptomycin sulfate.…”

Oudemansin, strobilurin A, strobilurin B and myxothiazol: new inhibitors of the bc1 segment of the respiratory chain with an E‐β‐methoxyacrylate system as common structural element

“…Antimycin and all other biochemical reagents were purchased from Boehringer (Mannheim). [6]. Submitochondrial particles from beef heart were prepared as in [2].…”