Properties and Cost Effective Method for Production of the Antitumor Agent Duclauxin from Sporulating Penicillium herquei

Abstract

Duclauxin, an antitumor agent, was isolated from sporulating Penicillium herquei (ATCC34665) grown on a medium of peanut hulls supplemented with potato starch solution (termed "Gostar"). The medium was inoculated with a sporulating subculture of P. herquei established on a 2% potato starch slurry supplemented with mineral salts. The P. herquei grew as well on Gostar as on an enriched medium. Duclauxin was isolated in crystalline form from Gostar-grown P. herquei. Comparison of costs of duclauxin obtained from inexpensive Gostar versus costly enriched media indicated that Gostar reduces production expenses. Duclauxin was not effective as an antibiotic against certain species of gram-positive and gram-negative bacteria, fungi, and viruses, but a concentration-dependent inhibition of wheat coleoptile growth was observed. Duclauxin was characterized by melting point, optical rotation, IR and NMR spectroscopy, MS and X-ray diffraction.

Fungal phenalenones: chemistry, biology, biosynthesis and phylogeny

“…The oligophenalenone dimer duclauxin (55), a lipophilic phenol compound with a lactone ring, has been reported as the metabolite of P. duclauxi, 83 P. herquei (ATCC 34665) 84 and P. stipitatum. 85 The full structure and absolute stereochemistry were determined by X-ray determination of monobromoduclauxin.…”

“…[88][89][90][91] Duclauxin ( 55) is not effective against Grampositive and Gram-negative bacteria, fungi, or viruses, but a concentration-dependent inhibition of wheat coleoptile growth has been reported. 84 Duclauxin (55) has also been reported as an inhibitor of respiration in tumor cells and isolated rat liver mitochondria, 92 having a marked uncoupling effect on oxidative phosphorylation by rat liver mitochondria at a dose of 25 nM mg À1 protein. 93 Growth inhibition of murine leukemia L-1210 culture cells by 55 and related compounds is in the order duclauxin z desacetylduclauxin > the semisynthetic N-methylduclauxamide > duclauxamide, meaning that 55 exhibited the strongest effect on mitochondrial respiration.…”

Duclauxin Derivatives From Fungi and Their Biological Activities

“…However, the yield of duclauxin ( 1 ) from Gostar medium (7.71 mg/flask) was less than enriched media (8.57 mg/flask). The cost comparison greatly favors the Gostar-type medium for this process ( Bryant et al, 1993 ). Fourteen in vitro growth media were used to cultivate the fungi to produce duclauxin analogs in the present report, showing that fungi have different compounds on different artificial growth media under different conditions ( Table 1 ).…”

“…It was observed that duclauxin ( 1 ) significantly inhibited the growth of etiolated wheat coleoptiles in a concentration-dependent manner. The percentage of inhibition at selected concentrations of duclauxin relative to controls were: 100% at 10 –3 M, 80% at 10 –4 M, 39% at 10 –5 M, and 0% at 10 –6 M ( Bryant et al, 1993 ; Table 6 ).…”

Four novel Talaromyces species isolated from leaf litter from Colombian Amazon rain forests

“…The anticancer agent duclauxin was first found in T. duclauxii, but this compound has also been reported from T. macrosporus (Shibata et al 1965;Frisvad et al 1990;Bryant et al 1993). Duclauxin was also reported from Penicillium herquei and P. manginii (Bryant et al 1993;Cao et al 2015), but the strains used had been misidentified, and the producers were Talaromyces species as well. Vermicillin is the third anticancer agent from T. amazonensis (Fuska et al 1979).…”