6ix3

The structure of LepI complex with SAMThe structure of LepI complex with SAM

Structural highlights

6ix3 is a 2 chain structure with sequence from Aspergillus flavus NRRL3357. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.13Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

LEPI_ASPFN O-methyltransferase; part of the gene cluster 23 that mediates the biosynthesis of a family of 2-pyridones known as leporins (PubMed:20447271, PubMed:26051490). The hybrid PKS-NRPS synthetase lepA and the enoyl reductase lepG are responsible for fusion of phenylalanine with a hexaketide and subsequent release of the stable tetramic acid precursor, pre-leporin C (PubMed:26051490). Because lepA lacks a designated enoylreductase (ER) domain, the required activity is provided the enoyl reductase lepG (PubMed:26051490). It is possible that the dehydrogenase lepF also participates in production of pre-leporin C (PubMed:26051490). Cytochrome P450 monooxygenase lepH is then required for the ring expansion step to yield leporin C (PubMed:26051490). Leporin C is then presumably further oxidized by the N-hydroxylase lepD to form leporin B (PubMed:26051490). LepI may possess a function in biosynthesis upstream of lepA (PubMed:26051490). Leporin B is further oxidized in the presence of ferric ion to give the leporin B trimer-iron chelate, but whether or not this reaction is catalyzed by an enzyme in the pathway or by ferric ion is not determined yet (PubMed:26051490).^[1] ^[2]

References

↑ Cary JW, Uka V, Han Z, Buyst D, Harris-Coward PY, Ehrlich KC, Wei Q, Bhatnagar D, Dowd PF, Martens SL, Calvo AM, Martins JC, Vanhaecke L, Coenye T, De Saeger S, Di Mavungu JD. An Aspergillus flavus secondary metabolic gene cluster containing a hybrid PKS-NRPS is necessary for synthesis of the 2-pyridones, leporins. Fungal Genet Biol. 2015 Aug;81:88-97. doi: 10.1016/j.fgb.2015.05.010. Epub 2015, Jun 4. PMID:26051490 doi:http://dx.doi.org/10.1016/j.fgb.2015.05.010
↑ Georgianna DR, Fedorova ND, Burroughs JL, Dolezal AL, Bok JW, Horowitz-Brown S, Woloshuk CP, Yu J, Keller NP, Payne GA. Beyond aflatoxin: four distinct expression patterns and functional roles associated with Aspergillus flavus secondary metabolism gene clusters. Mol Plant Pathol. 2010 Mar;11(2):213-26. doi: 10.1111/j.1364-3703.2009.00594.x. PMID:20447271 doi:http://dx.doi.org/10.1111/j.1364-3703.2009.00594.x

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OCA

[1] Cary JW, Uka V, Han Z, Buyst D, Harris-Coward PY, Ehrlich KC, Wei Q, Bhatnagar D, Dowd PF, Martens SL, Calvo AM, Martins JC, Vanhaecke L, Coenye T, De Saeger S, Di Mavungu JD. An Aspergillus flavus secondary metabolic gene cluster containing a hybrid PKS-NRPS is necessary for synthesis of the 2-pyridones, leporins. Fungal Genet Biol. 2015 Aug;81:88-97. doi: 10.1016/j.fgb.2015.05.010. Epub 2015, Jun 4. PMID:26051490 doi:http://dx.doi.org/10.1016/j.fgb.2015.05.010

[2] Georgianna DR, Fedorova ND, Burroughs JL, Dolezal AL, Bok JW, Horowitz-Brown S, Woloshuk CP, Yu J, Keller NP, Payne GA. Beyond aflatoxin: four distinct expression patterns and functional roles associated with Aspergillus flavus secondary metabolism gene clusters. Mol Plant Pathol. 2010 Mar;11(2):213-26. doi: 10.1111/j.1364-3703.2009.00594.x. PMID:20447271 doi:http://dx.doi.org/10.1111/j.1364-3703.2009.00594.x

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