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radP

Gene
radP
Protein
Cytochrome P450 monooxygenase radP
Organism
Chaetomium chiversii
Length
501 amino acids
Function
Cytochrome P450 monooxygenase; part of the gene cluster that mediates the biosynthesis of radicicol, a resorcylic acid lactone (RAL) that irreversibly inhibits the HSP90 molecular chaperone, an important target for cancer chemotherapy (PubMed:19101477). The cluster encodes only two apparent post-PKS enzymes, a cytochrome P450 monooxygenase (radP) and a non-heme halogenase (radH) that introduce the epoxide and the chlorine, respectively (PubMed:19101477). If this cluster includes all the genes required for radicicol biosynthesis, the remaining structural features of radicicol are presumably generated by the PKSs rads1 and rads2 (PubMed:19101477). The C-2' ketone could arise if the R-PKS rads1 and NR-PKS rads2 each carry out four iterations, in contrast to the five iteration-three iteration split for the hypothemycin PKSs (PubMed:19101477). The origin of the cis 5',6' double bond is not known (By similarity). The radicicol R-PKS rads1 ER domain may catalyze either double bond isomerization or reduction in the third iteration (By similarity).
Similarity
Belongs to the cytochrome P450 family.
Mass
57.108 kDa
Sequence
MAEFHPTAFLLPAAVTMIAGYFLCTALYNVYFHPLAKFPGPRLYAASQIPITIKRLLGDEVATFHKLHAKYGQFVRVAPGELSTINPAASRDVYGHRNPAKSIPKDFKAYYMKNQRRDGTEGLMTADDDLHRRQRKIFSPAFSDRAIREQEPLLKKYTDLLVEKAGVASDADGKVDMVMMFNFATFDFIADCVFGDSLHLLEKMEYNPFLANISAVVKFSAMRRAIRSFPYMDETFEKLIPASMKRKRMEHVKFCDDLVDRRLEKAVTNHPDFWTLVLRANEKGEGLTLGEMHQNSFLFLTAATETTSSLMSALTYLLCQNPDKMKKLVDEIRGRFKSTEEMTTVSLPPLEYLQMCIEEGLRVYPPVPGGLPRRVTADGASLDGRELPPDTVVYYAHYASYHSAAHFARPDEFHPERWASVPPSEFANDCRDAVIPFSAGPRDCIGKNLAYHEARLLLAKFLWTYDVELCEESKDWIKQKSFIVGVKRPLYVKLHRVVREK