Cycloheximide and acetoxy-cycloheximide specifically inhibit protein synthesis in L-cells growing in suspension culture. In extracts of rat liver, the drugs inhibit transfer of amino acid from soluble RNA to polypeptide. Unlike puromycin, these drugs do not accelerate release of nascent polypeptide chains. The drugs have no effect on protein synthesis in extracts of Escherichia coli.

https://science.sciencemag.org/content/sci/146/3650/1474.full.pdf

Cycloheximide: aspects of inhibition of protein synthesis in mammalian cells.

The Science of Antibiotic Discovery.

SUMMARY: The rates of utilization of energy-yielding substrates (glucose and oxygen) by Penicillium chrysogenum in glucose-limited chemostat cultures were resolved into requirements or ‘rations’ for growth and maintenance. The maintenance ration of glucose was almost all oxidized to carbon dioxide. Over the growth rate range 0.023--0.075 hr-1 only vegetative growth occurred; although the filamentous growth form predominated, the occurrence of pellets and swollen organisms increased with growth rate. At growth rates of 0.014 hr-1 and below, conidiation occurred and was maximal at a specific growth rate of 0.009 hr-1 (average doubling time 78 hr). After growth in chemostat culture the organism could be maintained in a non-growing state by supplying only the maintenance ration of glucose (0.022 g. glucose g. mycelial dry wt/hr). When growth in the chemostat was suddenly stopped by stopping the glucose feed, the mould autolyzed; autolysis was prevented by supplying the maintenance ration of glucose. When the glucose feed rate in chemostat cultures was decreased to the maintenance ration, mycelial differentiation occurred. Differentiation involved increased hyphal vacuolation, a decreased degree of oxidation of glucose, breakdown and resynthesis of nucleic acids and conidiation. The rates at which these changes occurred were inversely related to the growth rate prior to stopping growth. For maximum conidia formation there was an optimal glucose feed rate about 0.038 g. glucose/g. mycelial dry wt/hr, that is 1.7 x maintenance ration. The maintenance ration of glucose was shown to play a role in preventing autolysis and facilitating conidiation. Electron microscope studies showed that there was no change in the observed ultrastructure of cells (except degree of vacuolation) with change in specific growth rate from near the maximum to zero. The septa of the hyphae were found to be plugged.

/pdf/the-influence-of-maintenance-energy-and-growth-rate-on-the-3k3pfepyij.pdf

The Influence of Maintenance Energy and Growth Rate on the Metabolic Activity, Morphology and Conidiation of Penicillium chrysogenum

Invivo differentiation of yeast cytoplasmic and mitochondrial protein synthesis with antibiotics

The antifungal compound actidione has been found to inhibit both nucleic acid and protein synthesis in Saccharomyces carlsbergensis. At the minimum growth inhibitory concentration synthesis of deoxyribonucleic acid and protein is completely inhibited, whereas the synthesis of ribonucleic acid continues for some time after the addition of the antibiotic to the culture. Some other antifungal agents were found to inhibit both nucleic acid and protein synthesis, but in no case was any differential effect obtained.

The effect of actidione and other antifungal agents on nucleic acid and protein synthesis in Saccharomyces carlsbergensis.

Actidione is a chloroformand water-soluble antibiotic that is produced by streptornycin-yielding cultures of Streptomyces griseus and that, unlike streptomycin, possesses no marked antibacterial activity (Whiffen, Bohonos, Emerson, 1946). It is, however, highly active against a large number of yeasts, including the pathogen Cryptococcus neoformans. Actidione has been obtained in pure crystalline form (Leach, Ford, and Whiffen, 1947) and its empirical formula has been determined (Leach and Ford, 1948). The purpose of this paper is to report studies on the production, assay, and antibiotic activity of actidione. The production by the same organism of twvo easily differentiated antibiotics has offered an opportunity for the study of several problems of theoretical interest. It has been possible to determine the effect of changes in the composition of the fermentation medium upon the relative yields of actidione and streptomycin and to demonstrate that the amounts of the two antibiotics produced may vary independently of one another. It was of further interest to determine whether or not the loss by mutation of the ability to synthesize one antibiotic would result in an inability to synthesize the other antibiotic.

The Production, Assay, and Antibiotic Activity of Actidione, an Antiobiotic from Streptomyces griseus

Saccharomyces cerevisiae ATCC 918................ 2,500,000 <1,000 Cryptococcus neoforman ............... ............ 1,300,000 <1,000 Rhodotorula ep. ................................... 1,300,000 1,000 Hormodendrum pedrosoi 275........................ 20,000 <1,000 Monosporium apiospermum........................ 20,000 <1,000 Phialophora verrucosa............................. 20,000 <1,000 Blastomyces dermatitidis 930....................... <10,000 <1,000 Candidd albicans.................................. <10,000 ' <1,000 Coccidioides immitis 819........................... <10,000 <1,000 Epidermophyton floccosum......................... <10,000 <1,000 Geotrichum sp..................................... <10,000 <1,000 Hormodendrum compactum ......................... < 10,000 <1,000 Nocardia asteroides653.<10,000 <1,000 Sporotrichum schenkii ................ ............. < 10,000 <1,000 Trichophyton rubrum ............... ............... < 10,000 <1,000 Bacillus subtilis .................................... <10,000 28,000,000 Staphylococcus aureus FDA 209.................... <10,000 21,000,000 Escherichia coli .................................... <10,000 3,500,000 Pseudomonas aeruginosa ATCC 9027............... <10,000 350,000

The Production of an Antifungal Antibiotic by Streptomyces griseus.

(1950) The Activity in Vitro of Cycloheximide (Acti-Dione) Against Fungi Pathogenic to Plants Mycologia: Vol 42, No 2, pp 253-258

The Activity in Vitro of Cycloheximide (Acti-Dione) Against Fungi Pathogenic to Plants

One of the important factors bearing on the increased commercial production ofpenicillin has been the successful selection of strains of the Penicillium notatumchrysogenum group that have superior penicillin-producing ability (Raper and Alexander, 1945; Gailey et al., 1946). Of almost equal importance is the maintenance of these strains in a state of maximal penicillin production. A number of workers, Foster et al. (1943), Waksman and Reilly (1944), and Raper and Alexander (1945), have observed and reported the tendency of P. notatum to yield decreasing amounts of penicillin upon serial subculture. We have found one strain of this fungus to lose its penicillin productivity with such regularity that study of the phenomenon seemed warranted. With no name for this phenomenon in common use we have chosen to call it "penicillin run-down." Methods for minimizing the "run-down" of penicillin-producing cultures have been published (Raper and Alexander, 1945; Foster et al., 1943), but quantitative data have not been presented on the rate and extent of penicillin run-down and on conditions influencing its occurrence. It is the purpose of this paper to describe experiments pertaining to penicillin run-down in P. notatum, NRRL 1249.B211 and to describe our efforts to increase the penicillin yield of this strain by a program of selection and testing.

The Relation of Natural Variation in Penicillium notatum to the Yield of Penicillin in Surface Culture.

The spontaneous transition in Allomyces arbuscula from a sporo? phytic to a gametophytic state without the intervention of the resistant sporangium and its meiospores has been previously re? ported by Sorgel (1937). What appears to be a similar vegeta? tive transformation of a sporophytic plant into a gametophytic plant has been consistently effected by treatment of the sporophyte of A. arbuscula with the antibiotic cycloheximide. The purpose of this paper is to describe and discuss the nature of the transforma? tion induced by cycloheximide.

Alma J. Whiffen

Papers

The Production, Assay, and Antibiotic Activity of Actidione, an Antiobiotic from Streptomyces griseus

The Production of an Antifungal Antibiotic by Streptomyces griseus.

The Activity in Vitro of Cycloheximide (Acti-Dione) Against Fungi Pathogenic to Plants

The Relation of Natural Variation in Penicillium notatum to the Yield of Penicillin in Surface Culture.

The Effect of Cycloheximide on the Sporophyte of Allomyces Arbuscula