Production of cyclochlorotine and a new metabolite, simatoxin, by Penicillium islandicum Sopp

Abstract

Production of the hepatotoxin cyclochlorotine by Penicillium islandicum was studied under a variety offermentation conditions. The best system for production was agitated red wheat. A thin-layer chromatographic method was developed for the detection of this cyclic polypeptide. These experiments have resulted in the isolation of a new toxic metabolite, which we call simatoxin.

Polyphasic taxonomy of the genus Talaromyces

“…Extrolites : 3-hydrophthalic acid ( Gatenbeck 1957 ), islandicin = 1,4,5-trihydroxy-2-methylanthraquinone ( Howard 1948, Howard & Raistrick 1949 ); chrysophanic acid ( Howard & Raistrick 1950 ); skyrin and flavoskyrin ( Howard & Raistrick 1954a ); iridoskyrin and (−)-rubroskyrin ( Howard & Raistrick 1954b, Takeda et al 1973 ), endocrocin ( Gatenbeck 1959 ), emodin ( Gatenbeck 1958, Sankawa et al 1973, Kawai et al 1984 ); (−)-luteoskyrin ( Yamamoto et al 1956, Ueno & Ishikawa 1969, Takeda et al 1973, Ghosh et al 1978a ); (−)-rugulosin ( Takeda et al 1973 ); erythroskyrine ( Howard & Raistrick 1954b, Shoji et al 1965, Shibata et al 1966, Kenkyusho 1983 ); 1,4,7,8-tetrahydroxy-2-anthraquinone, chrysophanol, catenarin and dimers of those and emodin and islandicin: dianhydrorugulosin, dicatenarin, roseoskyrin, auroskyrin, rhodoislandicin A & B, punicoskyrin, aurantioskyrin, oxyskyrin, skyrinol, (−)-deoxyrubroskyrin, (−)-deoxyluteoskyrin, (−)4a-oxyluteoskyrin ( Ogihara et al 1968, Takeda et al 1973 ); islandic acid I & II ( Fujimoto et al 1982 ); pibasterol ( Ghosh et al 1978a ); cyclochlorotine = islanditoxin = chlorine containing peptide = chloropeptide and simatoxin ( Marumo & Sumiki 1955, Uraguchi et al 1961, 1972, Ghosh et al 1978b ). Extrolites detected in this study (in CBS 338.48 T ; NRRL 1036; CBS 165.81; IBT 12697; IBT 15605; FRR 3445; FRR 3606; CBS 189.68 and CBS 117284): erythroskyrin, islandicin, luteoskyrin, mitorubrinic acid and other special mitorubrins, rugulosin & skyrin.…”

Synthetic and Therapeutic Applications of Ammonia-lyases and Aminomutases

“…being the only known ( R )-selective and phenylalanine specific mutases for a long time, there have always been clues hinting at the existence of analogous enzymes in other organisms (Scheme a). Such evidence includes the occurrence of other metabolites containing ( R )-β-phenylalanine, the most notable examples of these being the chemically similar astins and cyclochlorotines from the plant Aster tataricus and fungus Talaromyces islandicum respectively. , Although these bioactive pentapeptides were isolated and characterized decades ago, knowledge of their biosynthesis was hindered by the lack of genome sequence data. With the recent release of the T. islandicum genome, the biosynthetic gene cluster associated with cyclochlorotine production could be identified .…”

Kinetic Resolution of Aromatic β‐Amino Acids Using a Combination of Phenylalanine Ammonia Lyase and Aminomutase Biocatalysts

“…[5] The lack of characterisation with this class of enzyme is surprising given the detailed structural and biochemical knowledge of known enzymes [6][7][8][9][10] and the wealth of organisms shown to produce βphenylalanine-containing compounds. [2,[11][12][13][14] Progress in this area is likely hindered by the poor quality of enzyme sequence annotations in biological databases a fact which itself precludes correct identification biosynthetic pathways for known and novel bioactive molecules applicable to medical research. This problem has already been highlighted within this particular enzyme family by efforts to uncover novel aminomutases specific to tyrosine (TAMs).…”