A complex of 18-membered macrolide antibiotics has been discovered in the fermentation broth of strain AB718C-41. The producing culture, isolated from a soil sample collected in Hamden,Connecticut, was identified as a strain of Dactylosporangium aurantiacum and was designated D. aurantiacum subsp. hamdenensis subsp. nov. The antibiotic complex was produced in a NewBrunswick 150-liter fermentor using a mediumconsisting of glucose, soybean oil, soybean flour, beef extract and inorganic salts. Several of the antibiotics were active against sensitive and multiple antibiotic-resistant strains of pathogenic Gram-positive bacteria.

Determination of the mechanism of action of FK506and cyclosporin A has yielded new molecular targets involved in signal transduction during T cell activation. A commontarget of FK506 and cyclosporin A is inhibition of activation of the NFATtranscription factor, for which a specific binding region is present in the promoter of the IL-2 gene. A reporter gene assay has been used to screen for agents that interfere with this early step in T cell activation. Simple aromatic compoundsthat block NFAT-dependent transcription and showin vitro immunosuppressiveactivity were isolated from the broth and mycelia of two Streptomyces sp. fermentations. The compounds were active at concentrations that were not directly cytotoxic.

The ardeemins are a new family of secondary metabolites produced by submerged fermentation of a fungus which was isolated from a soil sample collected in Brazil. Based on taxonomic studies, the producing culture was identified as Aspergillus fischeri var. brasiliensis strain AB 1826M-35. 5-7V-Acetylardeemin potentiated the cytotoxicity of the anticancer agent vinblastine in multidrug resistant humantumorcells.Multidrug resistance (MDR)is characterized by the development of resistance to several structurally unrelated anticancer agents and is a major cause of failure of cancer chemotherapy. The appearance of a specific glycoprotein, P-170, is generally associated with resistant cells1*. P-170 is a membrane associated glycoprotein thought to actively export cytotoxic compoundssuch as anthracyclines and Vinca alkaloids from resistant tumor cells2). Although several compoundsare knownto reverse MDR, none are used clinically because of adverse side effects3*. In the course of screening for modulators of MDR, we discovered a family of novel compounds which we have called ardeemins. 5-JV-Acetylardeemin appears to be the most efficacious of these compoundsin the reversal of MDR. The compoundsare produced in the fermentation broth of Aspergillus fischeri var. brasiliensis strain AB 1826M-35. This paper describes the taxonomy and the fermentation of the producing microorganism and the biological activity of ardeemin and 5-7V-acetylardeemin. The isolation and structural elucidation of these and other congeners are described in an accompanying publication4*. Materials and Methods MicroorganismsStrain AB1826M-35 was isolated from soil collected in Brazil. A subculture of the microorganism was deposited at

The pacidamycins are a new complex of nucleosidyl-peptide antibiotics with highly specific activity against Pseudomonas aeruginosa. They are produced by Streptomyces coeruleorubidus AB 1 183F-64 which was isolated from a soil sample collected at Offenburg in the FRG. The mature spore masses of the producing organism are greenish gray to blue, and the spore chains are arranged in spirals. After the structures of the pacidamycins were determined, the fermentation medium was supplemented with component amino acids. This resulted in the directed biosynthesis of several members of the complex. The overall antibiotic recovered was increased from 1~2 mg/liter to more than 100 mg/liter through a combination of strain selection, mediummanipulation and amino acid feeding experiments.