Fungal Metabolism of Dichloronitrobenzenes

Abstract

Metabolism of 2,3-, 2,4-, 2,5-, 2,6-, 3,4-and 3, 5-dichloro-l-nitrobenzenes by Mucor javanicus and metabolites of 2,4-dichloro-l-nitrobenzene (2,4-DCNB) by seven fungi were investigated. The dichloronitrobenzenes were reduced predominantly to the corresponding benzenamines by M., javanicus. In addition to the benzenamine derivatives, minor metabolites in which an ortho-chlorine atom was substituted with a methylthio group were detected in the medium of M. javanicus administered 2,3-and 2,4-DCNB. More or less amounts of 2,4-dichlorobenzenam.ine and 4-chloro-2-methylthio-l-nitrobenzene were detected as metabolites of 2,4-DCNB also in the media of 1V7. griseo-cyanus, M. hiemalis, M. praini and Aspergillus flavus. * Microbial Metabolism of Chlorinated Nitrobenzenes (Part 2). Part 1, see Ref. 1). ** To whom reprint requests should be addressed.

Metabolic Pathways of 2, 4-Dichloro-1-nitrobenzene in <i>Mucor javanicus</i>

“…The latter pathway through microbial metabolism of xenobiotics such as 2, 4-and 2, 3-DCNB was confirmed for the first time in M. javanicus. The significance of the reversible transformation of a cysteine conjugate (3) to N-acetyl-S-(5-chloro-2-nitrophenyl)cysteine (7, a mercapturic acid known as a major metabolite of the glutathione conjugate in mammals and excreted in urine) in the fungus was not fully recognized. 13) Generally a glutathione conjugate is formed by reaction of an electrophilic carbon atom with nucleophilic glutathione (GSH), which is catalyzed by an enzyme glutathione S-transferase (GST).…”

“…(2), S-(5-chloro-2-nitrophenyl)cysteine (3), 5-chloro-2-nitrobenzenethiol (4), 4-chloro-2-methylthio-l-nitrobenzene (5), 4-chloro-2-methylthiobenzenamine (6), N -acetyl-S -(5-chloro -2-nitrophenyl)cysteine (7), 5-chloro-2-methylsulfinyl-l-nitrobenzene (8), 5-chloro-2-methylsulfonyl-l-nitrobenzene (9), 5-chloro-2-methylsulfinylbenzen-amine (10), 5-chloro-2-methylsulfonylbenzenamine (11) and 2, 4-dichlorobenzenamine (12) were obtained as described previously. [1][2][3] Bis(5 chloro-2-nitrophenyl) disulfide (13). Disulfide 13 was obtained as a by-product from the preparation of 5.…”

A Glutathione Conjugate of 2, 4-Dichloro-1-nitrobenzene: Its Detection as a Metabolic Intermediate and Further Metabolism in <i>Mucor javanicus</i>

“…Quantitative and qualitative analyses of volatile metabolites were conducted as shown in our previous papers. 1,2) Metabolism by the resting cells: The fungus grown for 4 days in the basal medium was harvested by filtration and sucked dry on a Buchner funnel (75-76% moisture). The mycelia were suspended in a reaction medium consisting of 67 mM phosphate buffer (pH 7.…”

“…Conjugate (2) in the Cell free System of Mucor javanicus Glutathione S-transferase (GST, EC 2, 5, 1, 18) with wide substrate-specificity which has been implicated in detoxification of xenobiotics by mammals, plants and insects11,12) has been recently found in microorganisms as well, such as Escherichia coli, 13) Cunninghamella elegans14' and Fusarium oxysporum. 15)…”

“…tabolites from a 2, 4-DCNB Glut athione Conjugate (2) and Its Related Compounds Synthetic substrates, glutathione and cysteine conjugates of 2, 4-DCNB (2 and 3) and 5-chloro-2-nitrobenzenethiol (4), which could be intermediates when 2, 4-DCNB metabolizes to methylthio-containing products (5 and 6), were fed to the growing cultures of M. javanicus. To the fungus grown for 4 days was added each substrate, and the resulting methylthio-containing metabolites were analyzed by GLC and GC-MS after 24 hr of incubation.…”