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FUM15

Gene
FUM15
Protein
Cytochrome P450 monooxygenase FUM15
Organism
Gibberella moniliformis (strain M3125 / FGSC 7600)
Length
596 amino acids
Function
Cytochrome P450 monooxygenase; part of the gene cluster that mediates the biosynthesis of fumonisins B1 (FB1), B2 (FB2), B3 (FB3), and B4 (FB4), which are carcinogenic mycotoxins (PubMed:12620260). On the basis of the chemical structures of fumonisins and precursor feeding studies, fumonisin biosynthesis is predicted to include at least five groups of biochemical reactions: synthesis of a linear polyketide with a single terminal carbonyl function and methyl groups at C-10 and C-14; condensation of the polyketide with alanine; reduction of the polyketide carbonyl to a hydroxyl; hydroxylation of 2-4 polyketide carbons; and esterification of six-carbon tricarboxylic acids to two of the hydroxyls (PubMed:12620260). The biosynthesis starts with the polyketide synthase FUM1-catalyzed carbon chain assembly from one molecule of acetyl CoA, eight molecules of malonyl CoA, and two molecules of methionine (PubMed:10413619). The C-18 polyketide chain is released from the enzyme by a nucleophilic attack of a carbanion, which is derived from R-carbon of alanine by decarboxylation, on the carbonyl carbon of polyketide acyl chain (PubMed:15137825, PubMed:12720383). This step is catalyzed by a pyridoxal 5'-phosphate-dependent aminoacyl transferase FUM8 (PubMed:15137825, PubMed:12720383). The resultant 3-keto intermediate 2-amino-3-oxo-12,16-dimethylicosane is then stereospecifically reduced to the 3-hydroxyl product 2-amino-3-hydroxy-12,16-dimethylicosane by reductase FUM13 (PubMed:12720383, PubMed:15137825). Subsequent oxidations at C-5, C-10, C-14 and C-15 followed by tricarballylic esterification of the hydroxyl groups on C-14 and C-15 furnish the biosynthesis of fumonisins (PubMed:15066782, PubMed:15137825, PubMed:16489749). The C-10 hydroxylation is performed by the cytochrome P450 monooxygenase FUM2 and occurs early in the biosynthesis (PubMed:16536629). The C-5 hydroxylation is performed by the dioxygenase FUM3 and occurs late in the biosynthesis (PubMed:20237561, PubMed:15066782, PubMed:15137825, PubMed:16536629). Cytochrome P450 monooxygenases FUM6 and FUM15 may be responsible for the two remaining hydroxylations at positions C-14 and C-15 (PubMed:12620260). The FUM11 tricarboxylate transporter makes a tricarboxylic acid precursor available for fumonisin biosynthesis via its export from the mitochondria (PubMed:12620260). If the precursor is citrate, the FUM7 dehydrogenase could remove the C-3 hydroxyl of citrate to form tricarballylic acid either before or after the CoA activation by the FUM10 acyl-CoA synthetase and FUM14 catalyzed esterification of CoA-activated tricarballylic acid to the C-14 and C-15 hydroxyls of the fumonisin backbone (PubMed:16489749, PubMed:17147424). Alternatively, if the precursor is cis-aconitate, FUM7 may function to reduce the double bond (PubMed:17147424). In this alternate proposal, feeding studies with tetradehydro-fumonisin B1 suggests that FUM7 cannot function on the tricarballylic ester and must therefore act before the FUM14-mediated esterification (PubMed:17147424).
Similarity
Belongs to the cytochrome P450 family.
Mass
67.191 kDa
Sequence
MRGLNNIAVALALSAIWSFGLDLGRHGTSGSSLLLALFRTLCKAYPFVVISHFVWSAIIWPTFFSPLRQLPNVPSDGWLSKETLRLVSEPRGVPQSDWINSLSNRPVDLARYRSFLGFERLLIISPKALAEVLTTKSYDFRKPGLIVSELKQATGMGVLLAEGSEHKSQRKALQTAFNYRHIKNLYPVFWDVAGEFATVLEKQIPTGTPRTSDTTAVIDIVDWASRATLDIIGRAGMGQGFDAIQNDDSRLHQAYRMIFEPSRGAIFLALLRLIFPERLVNWLPLRRNKRMRHGIQVIRSKCQELIRERKEKIKRQKAGVDNSGNDILTVALLNGVFTDEQLIDQLMTFLAAGHETTATALTWAIYILCKQPEVQNRLREEIRMHFPNPKGWPRSERPSSNTLQQAIDFKLPYLNVVCLEVMRYFAPIPLTMREATCDTTILHTFVPAGTRIILAPRVTNRDSALWGPDANNFNPDRWLSPKNGNREATEQSKFKIGNQKRDSTAAPEVTQEEVRGRTEARSNYADLTFLHGPRSCIGQSFARVEFAILLATLIANFEFQIEDESLLDERNISISRGATSRIVGGLKVRVRPIAVV