Polyketide transferase; part of the gene cluster that mediates the biosynthesis of fumagillin, a meroterpenoid that has numerous biological activities including irreversible inhibition of human type 2 methionine aminopeptidase (METAP2) (PubMed:23488861, PubMed:24568283). The pathway begins with the conversion of farnesyl pyrophosphate (FPP) to beta-trans-bergamotene by the membrane-bound beta-trans-bergamotene synthase af520 (PubMed:23488861). The initial oxidation of beta-trans-bergamotene by the multifunctional cytochrome P450 monooxygenase af510 involves C-H hydroxylation at the bridgehead C5 position to yield 5R-hydroxyl-beta-trans-bergamotene (PubMed:24568283). Subsequently, a four electron oxidation initiated at C-9 coupled to cleavage of the cyclobutane C5-C8 bond of the bicyclo[3.1.1] core yields the epoxyketone intermediate 5-keto-cordycol (PubMed:24568283). An additional epoxidation reaction also catalyzed by af510 then furnishes the characteristic bisepoxide ketone 5-keto-demethoxyfumagillol (PubMed:24568283). 5-keto-demethoxyfumagillol is then subjected to successive C-6 hydroxylation and O-methylation by the dioxygenase af480 and O-methyltransferase af390-400, respectively, to yield 5-keto-fumagillol, which is then stereoselectively reduced by the keto-reductase af490 to 5R-hydroxy-seco-sesquiterpene (PubMed:24568283). The next step is the polyketide transferase af380-catalyzed transfer of a dodecapentaenoyl group synthesized by the polyketide synthase af370 onto 5R-hydroxy-seco-sesquiterpene which leads to the production of prefumagillin (PubMed:24568283). Finally, oxidative cleavage by the monooxygenase af470 converts prefumagillin to fumagillin (PubMed:24568283).

Belongs to the polyketide transferase af380 family.

292 amino acids

MNREDVEFPTCDGLILRGWLYPGTIRGPAIVMNQGFNTPKEILLPDVAVWFQQQGVTVLLYDNRCIGASDGEPRNDVKPAKLVEDFHDALTFMARHPMVDEDKIILYGYSFSAMTALVAAGLDHRVGAAISVTPIANYDFREKEKNNVMALAMQDRVSTLAGNDPVYIPFVGDDGYNPAGWGNQYNMEQFRAFLGTSFFTNRTTVQSYYHVLAWQPYGAMRLIKGTPVMMVTPAEDTISSPADQRAVFDMIPEPNKEFDLVAGRGHMDVINGEGAEEVLQRQLAFMRKHLDF

32.7 kDa

(Note: Representative image - actual molecular weight may vary depending on tag type and expression method)

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