Sterigmatocystin biosynthesis

Yu, J.H. and Leonard, T.J., Sterigmatocystin biosynthesis in Aspergillus nidulans requires a novel type I polyketide S5mthase, J. Bacterial., 177, 4792, 1995. 

Feng, G. IT., and Leonard, T. J. (1998). Culture conditions control expression of the genes for aflatoxin and sterigmatocystin biosynthesis in Aspergillus parasiticus and A. nidulans. Appl. Environ. Microbiol. 64, 2275-2277. 

Kelkar, H.S., T.W. Skloss, J.F. Haw, N.P. Keller, and T.H. Adams (1997). Aspergillus nidulans stcL encodes a putative cytochrome P-450 monooxygenase required for bisfuran desaturation during aflatoxin and sterigmatocystin biosynthesis. J. Biol. Chem. 272, 1589-1594. 

KELLER, N.P., WATANABE, C.M.H., KELKAR, H.S., ADAMS, T.H., TOWNSEND, C.A., Requirement of monooxygenase-mediated steps for sterigmatocystin biosynthesis by Aspergillus nidulans, Appl. Environ. Microbiol., 2000, 66, 359-362. 

KLICH, M.A., MULLANEY, E.J., DALY, C.B., CARY, J.W., Molecular and physiological aspects of aflatoxin and sterigmatocystin biosynthesis by Aspergillus tamarii and A. ochraceoroseus, Appl. Microbiol. BiotechnoL, 2000, 53, 605-609. 

GUZMAN-DE-PENA, D., AGUIRRE, J., RUIZ-HERRERA, J., Correlation between the regulation of sterigmatocystin biosynthesis and asexual and sexual sporulation in Emencella nidulans, Antonie Leeuwenhoek, 1998, 73, 199-205. 

The direct desaturation of carbon adjacent to heteroatoms, notably oxygen and nitrogen, has also been observed. These reactions include the desaturation of a tetrahydrofuran ring in the biosynthesis of aflatoxin and sterigmatocystin by a specific P450 enzyme, the P450-catalyzed desaturation of flavanones to flavones, and the conversion of ethylcarbamate to vinyl carbamate . In some instances, the desaturation may involve the carbon and the heteroatom instead of two carbon atoms. The CYP2B1-catalyzed oxidation of testosterone to androstenedione, which involves oxidation of the 17-hydroxy to a 17-keto function, is possibly such a reaction, because only... 

YABE, K., MATSUSHIMA, K., KOYAMA, T., HAMASAKI, T., Purifieation and characterization of O-methyltransferase 1 involved in conversion of demethylsterigmatocystin to sterigmatocystin and of dihydrodemethylsterigmatocystin to dihydrosterigmatoeystin during aflatoxin biosynthesis, Appl Environ. Microbiol., 1998,64,166-171. 

BiosyntheticaUy, the aflatoxins are all formed from the same precursor, versiconal hemiacetal acetate (12) (25). Compound 12 is formed from acetate, the units of which are converted into a polyketide. The polyketide is then metabolized to the xanthone 12 (see Scheme 2.1) (26). Intermediate 12 can then be transformed either into versicolorin A (13) or versicolorin B (14) in several steps. Versicolorin A (13) may be converted to sterigmatocystin (15), while 14 can lead to dihydro-sterigmatocystin (16). Sterigmatocystin (15) can be metabolized to aflatoxins Gi (3) or Bi (1) and the latter may then be transformed to aflatoxin Mi (5). Aflatoxins B2 (2) and G2 (4) are formed from dihydrosterigmatocystin (16) and aflatoxin M2 (6) is formed by conversion from B2 (2). Pathways also exist to convert aflatoxin Bi (1) to B2 (2), Ml (5) to M2 (6), and Gj (3) to G2 (4), and vice versa. Important biosynthesis steps are shown in Scheme 2.1. 

Sterigmatocystin (15) is both a carcinogenic hepatotoxin and a biosynthetic precursor to the important mycotoxin, aflatoxin, and, as such, its biosynthesis pathway has been studied quite extensively (607-608). This is purported to begin with a single C20 polyketide unit, which is folded in only one mode to form averufin (103) and then sterigmatocystin (15) (609). The authors provided evidence to support the identity of this compound through the synthesis of a common product from both it and from a... 

Fig. 13.7 Sterigmatocystin derivatives used by Townsend et al. to investigate the biosynthesis of aflatoxins...

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