Adriamycin, 14-hydroxydaunomycin, a new antitumor antibiotic from S. peucetius var. caesius. Reprinted from Biotechnology and Bioengineering, Vol. XI, Issue 6, Pages 1101-1110 (1969).

Streptomyces peucetius var. caesius, obtained from S. peucetius, the daunomycin producing microorganism, by mutagenic treatment, differs from the parent culture by the color of the vegetative and aerial mycelia and by its antibiotic producing ability. S. peucetius var. caesius accumulates adriamycin in submerged and aerated culture on a medium containing glucose, brewer's yeast, and inorganic salts both in shake flasks and in stirred fermenters. Isolation of the product is performed by solvent extraction, chromatography on buffered cellulose columns, and crystallization as the hydrochloride. The new antitumor agent, adriamycin, is the 14-hydroxy derivative of daunomycin.

New anthracycline glycosides: 4-O-demethyl-11-deoxydoxorubicin and analogues from Streptomyces peucetius var. aureus.

The new anthracyclines 4-O-demethyl-11-deoxydoxorubicin, 4-O-demethyl-11-deoxydaunorubicin along with its 13-dihydro and 13-deoxo analogues are the main components of the anthracycline complex produced by cultures of Streptomyces peucetius var. aureus. They were isolated by solvent partition, separated by column chromatography and characterized by chemical and physical methods. Among these new anthracyclines, displaying antibacterial and cytotoxic activity "in vitro", 4-O-demethyl-11-deoxydoxorubicin and the corresponding daunorubicin analogue were also active against experimental tumors.

New anthracycline glycosides from Micromonospora. I. Description of the producing strain.

During the course of successive mutagenic treatments of Streptomyces peucetius var. caesius, producer of anthracyclines, a novel mutant was isolated from a plate of the surviving population. This mutant showed remarkable morphological, cultural and biochemical differences when compared to the original strain. The new culture produced four new glycosides of a novel class within the group of the daunorubicin related anthracyclines, two of which were also present in the original strain. To our surprise the taxonomical study carried out on this mutant allowed its assignment to the genus Micromonospora ORSKOVA (1923). The possibilities of whether this new strain has originated from a contamination or from a mutation are discussed. The type strain is Micromonospora sp. strain B211 F.I. (identical to ATCC 31366; DSM 1190; FRI 4363).

Directed biosynthesis of analogues of ergot peptide alkaloids with Claviceps purpurea.

Analogues of peptide ergot alkaloids can be obtained by feeding a producing culture of Claviceps purpurea with an analogue of one of the amino acids of the peptide chain of the alkaloid.

Production of peptide ergot alkaloids in submerged culture by three isolates of Claviceps purpurea.

Three strains of Claviceps purpurea (Fr.) Tul., isolated from sclerotia grown on rye, produce under submerged conditions ergocryptine and ergotamine, ergocornine and ergosine, and ergocristine, respectively. All of the strains either lacked the ability to produce conidia or formed them sparingly, but they accumulated large quantities of lipids and sterols. The fermentations are typically divided into two phases. The first is characterized by the rapid utilization and exhaustion of the phosphate contained in the medium, rapid uptake of ammonium nitrogen and of citric acid, rapid growth, and low alkaloid production; the second phase is characterized by slower growth and by a marked accumulation of lipids, sterols, and alkaloids.

Ergotamine production in submerged culture and physiology of Calviceps purpurea.

Strain 275 FI of Claviceps purpurea, which produces large amounts of peptide alkaloids in submerged culture, and strains V, C, and W, spontaneously obtained from 275 FI and practically unable to produce alkaloids, were compared. Strain 275 FI differs from the other strains in its capacity to accumulate lipids and sterols, as well as in its capacity to produce alkaloids. Strain 275 FI utilizes large quantities of sucrose and citric acid simultaneously; strain V utilizes large amounts of sucrose but little citric acid; strain C utilizes large quantities of citric acid but only small amounts of sucrose; strain W consumes only small amounts of both substances. We conclude that the production of large quantities of alkaloids, as well as the accumulation of lipids and sterols, is correlated with the simultaneous utilization of large amounts of sucrose and citric acid.

Heterokaryosis and alkaloid production in Claviceps purpurea.

Strain 275 FI of Claviceps purpurea, which produces large amounts of peptide alkaloids in submerged culture, is a heterokaryon; after several generations on agar media, it segregates the single components. These components (by us labeled V, C, and W) are stable and produce almost no alkaloids under described conditions of submerged culture. The mycelium of strain 275 FI consists of hyphae with multinucleate cells and does not produce conidia. Strains V, C, and W form numerous anastomoses when grown together on agar. By combining strains V and C, a heterokaryon similar to 275 FI in appearance has been obtained. This new strain produces amounts of alkaloids much larger than those produced by V and C separately or in associated submerged culture. We conclude, therefore, that in strain 275 FI the heterokaryotic condition is favorable to the production of alkaloids. Several conidiaproducing cultures of C. purpurea of various origins, as well as sclerotia of the same species, have been examined. The results demonstrated that the heterokaryotic condition is rare in the cultures, but it is frequent in the mycelium from sclerotia. Since it is known that the production of alkaloids is typical of the sclerotial phase in C. purpurea, it is suggested that this capacity is related to the heterokaryosis of the producing strains.