Protein: Tricarboxylate transporter FUM11 (Fumonisin biosynthesis cluster protein 11) (Q8J2Q9)
Organism: Gibberella moniliformis (strain M3125 / FGSC 7600) (Maize ear and stalk rot fungus) (Fusarium verticillioides)
Function: Tricarboxylate transporter; part of the gene cluster that mediates the biosynthesis of fumonisins B1 (FB1), B2 (FB2), B3 (FB3), and B4 (FB4), which are carcinogenic mycotoxins. 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. 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. 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. This step is catalyzed by a pyridoxal 5'-phosphate-dependent aminoacyl transferase FUM8. 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. 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. The C-10 hydroxylation is performed by the cytochrome P450 monooxygenase FUM2 and occurs early in the biosynthesis. The C-5 hydroxylation is performed by the dioxygenase FUM3 and occurs late in the biosynthesis. Cytochrome P450 monooxygenases FUM6 and FUM15 may be responsible for the two remaining hydroxylations at positions C-14 and C-15. The FUM11 tricarboxylate transporter makes a tricarboxylic acid precursor available for fumonisin biosynthesis via its export from the mitochondria. 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. Alternatively, if the precursor is cis-aconitate, FUM7 may function to reduce the double bond. 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.
Subcellular location: Mitochondrion inner membrane {ECO:0000305}; Multi-pass membrane protein {ECO:0000255}.
Interaction partners:
Sequence:
MSLYDKSVTATRSAHRTSDTLHSLVAGSVAGGLEIAITYPAEFAKTRLQLNQVSGRNKQNVPWPRFGLQWYSGCIPFLIGNSVKTSIRFVSFDGYQKLLADDDGNISRFGILLAGFGAGATESLLAVTPSERIKTIIIEDRRLEKPRIRNSFHAMSIIARDHGLSGFFQGFWPTTARQSAGSAIRLGSYTFLKQVVQSRTPQGGKIGTVKTFIIGSLAGLITVYLTQPLDTIKTRMQRLEARTRYGNAFICARGILEQEGFTAFWSGAVARSLRLVMSGGIVFMVYEKVVEGLDVISPAKRYEIAA