Production of Griseofulvin by Some Strains of the Genus Penicillum

Abstract

Production of griseofulvin by some strains of the genus Penicillium was investigated. P. viridi-cyclopium Abe, P. brunneo-stoloniferum Abe, and P. nigricans var. sulfuratum Abe were compared with P. urticae known as griseofulvin-producing strain from the view point of industrial production of the antibiotic.

When these strains were surface cultured in a modified Czapek medium for 30 days at 28°C, they produced griseofulvin, and the strains of P. viridi-cyclopium were more potent than P. urticae. When P. viridi-cyclopium was incubated at 30°C for 2 weeks in the Czapek medium containing trace elements, production of the substance was 1,300–1,500 mcg/ml of culture filtrate, but in the medium without them the production was only about one-third of the medium containing them. A molasses medium containing cornsteep liquor gave a higher potency, 1,050 mcg/ml, at 1 week than in the Czapek medium, but the production was lower then after.

Ultraviolet absorption bands in ethanol solution of crude substance which was extracted from culture broth of the strain incubated in a molasses medium containing cornsteep liquor were observed at wave lengths of 233, 291, and 324 mμ, and were nearly identical with those of standard griseofulvin.

Griseofulvin is an antifungal antibiotic which was first isolated from the mycelium of Penicillium griseofulvum by Oxford, Raistrick & Simonart⁽¹⁾ in 1939. This substance is known to be active against fungal infections in plants, particularly Botrytis infections of lettuce and Alternaria blight of tomatoes.⁽²⁾ Recent reports^(3,4) revealed that griseofulvin has a high activity against infections of dermatophytic group-fungi, Trichophyton, Epidermophyton, and Microsporum, in man by oral medication.

The structure of griseofulvin was first established by Grove et al.⁽⁴⁾ in 1951. This substance has been produced by surface or submerged⁽⁵⁾ cultures of various species of the genus Penicillium: Penicillium griseofulvum Dierckx^(1,10), P. urticae Bainier⁽⁶⁾, P. patulum Bainier^(5,7), the above three are included in P. urticae by Raper and Thom⁽⁸⁾, P. janczewskii Zal(= P. nigricans (Bainier) Thom^(6,10,11), and P. raistrickii Smith⁽⁹⁾.

The present communication is concerned with preliminary investigation of the production of the antibiotic by several species of Penicillia which are preserved in the authors’ laboratory.