Fumonisins biosynthesis

Dalie, D., Pinson-Gadais, L., Atanasova-Penichon, V., Marchegay, G., Barreau, C., Deschamps, A., et al. (2012). Impact of Pediococcus pentosaceus strain L006 and its metabolites on fumonisin biosynthesis by Fusarium verticillioides. Food Control, 23, 405-411. 

CYP505 CO-1 to CO-3 fatty acid hydroxylations (P450foxy) and fumonisin C14 and CIS hydroxylations Fatty acid degradation and fumonisin biosynthesis F. oxysporum and F. verticillioides [504, 693, 694] [840, 841]... 

Wang, E. et ah, Inhibition of sphingolipids biosynthesis by fumonisin, implication for diseases associated with Fusariurn moniliforme, J. Biol. Chem., 266, 14486, 1991. 

Fumonisin inhibition of de novo sphingolipid biosynthesis (Merrill et ah, 2001 Riley et ah, 1996), resulting in depletion of complex glyco-sphingolipids, disruption of lipid rafts, and compromised folate transport via Folrl, which may have significant implications with respect to developmental anomalies such as NTDs (Hansen et ah, 2003 Piedrahita... 

Kobayashi S, Furuta T, Hayashi T, Nishijima M, Hanada K. Catalytic asymmetric syntheses of antifungal sphingofungins and their biological activity as potent inhibitors of serine palmitoyltransferase (SPT). J. Am. Chem. Soc. 1998 120 908-919. Merrill AH Jr, Gilchrist DG, Riley RT. Fumonisins and other inhibitors of de novo sphingolipid biosynthesis. Adv. Lipid Res. 1993 26 215-234. 

In spite of the importance of fumonisins, detailed molecular mechanism for their biosynthesis has just started to emerge in recent years. An understanding of the molecular mechanism is critical to the development of rational approaches to mycotoxin elimination in agriculture and food industry. This review intends to highlight the process in this area. 

The biosynthetic origin of fumonisins has been studied by several groups. C-3 to C-20 of the carbon backbone are derived fi om acetate, and C-1 and C-2, as well as the C-2 amino, are derived fi om alanine (17, 19). The two methyl groups at C-12 and C-16 are derived fi om methionine (20). Therefore, the biosynthesis of the carbon backbone of fumonisins is likely to involve a polyketide mechanism (27). The origin of the hydroxyl on the carbon backbone has also... 

Based on the paradigm of NRPS-catalyzed reactions, we proposed a mechanism for the biosynthesis of the tricarballylic esters of fumonisins (Figure 5). The first step is the ATP-dependent activation of a tricarboxylate substrate by FumlOp to form an acyl-AMP, which is subsequently transferred to the PCP domain of Fuml4p. The exact substrate for FumlOp is not known, but is likely to be an intermediate of the tricaroxylatic acid cycle 17). The data obtained from the FUM7 deletion mutant suggested that the substrate of FumlOp could be a... 

Proctor, R. H., Desjardins, A. E., Planner, R. D., and Hohn, T. M. (1999). A polyketide synthase gene required for biosynthesis of fumonisin mycotoxins in Gibberella fujikuroi mating population A. Fungal Genet. Biol. 27, 100-112. 

SHIM, W.B., WOLOSHUK, C.P., Nitrogen repression of fumonisin B biosynthesis in Gihherella fujikuroi, FEMS Microbiol. Lett., 1999,177, 109-116. 

For the final part (Scheme 5.3), the 20-carbon chain of fumonisin Bj was coupled from the Uthium acetylide derived from 273 and the Weinreb amide 279 (233). After enantioselective reduction of the alkynyl ketone 281 (234, 235), the C-10 stereochemistiy was set, followed by benzyl ether formation and acid-catalyzed acetonide removal, to provide diol 282 (236). Using tricarballylic acid dibenzyl ester, the two hydroxy groups were esterified (237) and the hydrogenation of the azide, the alkyne, and the benzylic ethers led to the target product, fumonisin Bj (249). The spectroscopic analysis matched with those of commercial fumonisin Bj and further experiments on the synthetic material showed inhibitoiy activity on sphingoUpid biosynthesis. 

Wang E, Norred WP, Bacon CW, Riley RT, Merrill Jr AH (1991) Inhibition of Sphingolipid Biosynthesis by Fumonisins. J Biol Chem 266 14486... 

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