Function
Cytochrome P450 monooxygenase; part of the gene cluster that mediates the biosynthesis of brefeldin A (BFA), a protein transport inhibitor that shows antiviral, antifungal, and antitumor properties (PubMed:24845309). The proposed biosynthesis of BFA involves formation of an acyclic polyketide chain that is differentially tailored throughout the backbone (PubMed:24845309). The highly reducing polyketide synthase Bref-PKS is proposed to synthesize the precisely reduced octaketide precursor, which could then be directly offloaded by the thiohydrolase enzyme Bref-TH followed by a cytochrome P450 monooxygenase-mediated formation of the cyclopentane ring and macrocyclization to afford 7-deoxy BFA. Alternatively, the first ring annulation can also occur on the ACP-tethered intermediate before the thiohydrolase release and lactonization (PubMed:24845309). The C7-hydroxylation by another cytochrome P450 monooxygenase is believed to be the final step in the process to obtain the final structure of BFA (PubMed:24845309). In addition to the HRPKS Bref-PKS and the thiohydrolase Bref-TH, the brefeldin A biosynthesis cluster contains 4 cytochrome p450 monooxygenases (called orf3 to orf6), as well a the probable cluster-specific transcription regulator orf8 (PubMed:24845309).
Sequence
MLALWVLAVALVAYFLCLSIYRLFLHPLANIPGPKLCALTGWYEVFWDIVVGGQFTFKIEEWHKTYGPVMRIGPNEVHFNDPDFYNELYTTTAAYQKPAEWRYRFGFGSALFDTVDHEHHAKRRAPLAAFFSRSKILEFSPFIQEQTDLLVQRIQEYEGQVICANEAFDALTMDIIGYYAFGLSYRSIDYPKFQAPCNHVTEDVARMVHTGAHFPWVFTILRSIPQAIVSLLAPPMKKIFKFNEEIAAQIRRILKNRVNLDQEKNFHRTIFHEILNSKLDPSELTQERLQMEAGSLVGAALETSKMTTALAIYYILAQPDVEKKLREELRTAMPDPGKILSVPELEQLPYLAACIREALRLAIGVSQRIRRYNPHAPTQYKNYTIPPNTVFGMCHWEQLRDARVWDRPYEFLPERWLANNGNPLALNGQPLAKYFVPFHRGPRGCLGKEMGMAQLNIGLATLFRRVDHLELFETDQSAVDIVADYFVPLCVKGSKGVRVLVK