A9145 is a basic, water-soluble, antifungal antibiotic which is produced in a complex organic medium by Streptomyces griseolus. The metabolite has a molecular weight of 510, and contains adenine as well as sugar hydroxyl and amino groups. Although glucose, fructose, glucose polymers, and some longchain fatty acid methyl esters supported biosynthesis, oils were superior, with cottonseed oil being preferred. Several ions and salts, especially Co2+, P043-, and CaCO3, were stimulatory. Adenine, nucleosides, and some amino acids increased the accumulation of A9145 in shaken-flask fermentors. Enrichment of the culture medium with tyrosine afforded maximal enhancement of antibiotic production in both flask and tank fermentors. Control of the dissolved 02 level was also critical, the optimal concentration being 3 x 10-2 to 4.5 x 10-2 ,mole of 02/ml. Optimization of various fermentation parameters increased antibiotic titers approximately 135-fold in shaken flask fermentors and 225-fold in stirred vessels.A new antifungal antibiotic, A9145, is produced by a strain of Streptomyces griseolus, NRRL-3739, isolated from a soil sample. This basic, water-soluble antibiotic has a molecular weight of 510, contains sugar hydroxyl and amino groups, and yields one mole of adenine upon mild acid hydrolysis (R. L. Hamill and M. M. Hoehn, Abstr. 11th Intersci. Conf. Antimicrob. Ag. Chemother., p. 21, 1971 Staley Manufacturing Co.), 1.5% Nutrisoy flour (Archer-Daniels-Midland Co.), 0.2% Nadrisol (National Distiller's Products Co.), 0.2% blackstrap molasses, 0.1% CaCO3, and 2.5% agar in distilled water (final pH 6.5).Fermentor inoculum. S. griseolus was transferred aseptically, as a lyophilized pellet containing approximately 2 x 106 spores, to 250-ml widemouth Erlenmeyer flasks. These flasks contained 50 ml of a seed medium composed of 1% glucose, 3% Dextrin 700, 1.5% Nutrisoy grits (Archer-DanielsMidland Co.), 0.5% Amber BYF 300 (Amber Laboratories), 0.5% blackstrap molasses, and 0.2% CaCO3, which had been adjusted to pH 6.5 and brought to 1 liter with tap water. Incubation was with agitation on a rotary shaker at 250 rev/min (5-cm stroke) at 30 C. After 30 hr, a second seed stage, 100 ml of the seed medium in a 1-liter flask, was inoculated from the first. After an additional 24-hr incubation period under the same conditions of temperature and agitation, the second seed stage was used to inoculate fermentors with a volume of the mycelial suspension equal to 1% (v/v) of the fermentation medium.Fermentors. In initial investigations, widemouth 250-ml Erlenmeyer flasks containing 50 ml of medium were used, and incubation was as previously described. Larger-volume fermentations for supply of the metabolite were conducted in fully baffled, stirred vessels of conventional design with a total capacity of 40 liters and a 1:1 height-diameter ratio for the 25 liters of medium. Dissolved oxygen content of the broth was monitored by use of a modification of a galvanic membrane electrode previously described (1)

A41030 is a complex of novel glycopeptide antibiotics produced by a culture isolated from a soil. Taxonomic studies have identified the microorganism, NRRL 15156, as a strain of Streptomyces virginiae. The major factor, A41030A, and three of the six minor factors are unique among glycopeptides in that they are naturally occurring aglycones, containing no neutral or amino sugars. The A41030 that was not spontaneously released into the fermentation broth could be released from the biomass into aqueous media at pH 10.5. In contrast to the vancomycin and N-demethylvancomycin fermentations, A41030 biosynthesis was stimulated by enriching the medium with KZHPO4 at a level of I mg/ml. Enrichment with putative precursors of the aglycone, however, did not increase the biosynthesis of A41030.