Function
Protostadienol synthase; part of the gene cluster that mediates the biosynthesis of helvolic acid, an antibacterial nortriterpenoid (PubMed:19415934, PubMed:19216560, PubMed:19951700, PubMed:29158519). Protostadienol synthase helA cyclizes (3S)-oxidosqualene to (17Z)-protosta-17(20),24-dien-3-beta-ol (protostadienol)(PubMed:19415934, PubMed:19216560, PubMed:19951700, PubMed:29158519). The synthesis of protostadienol is followed by several steps of monooxygenation, dehydrogenation, and acyl transfer to yield the final helvolic acid (PubMed:19216560). Following the cyclization to the tetracyclic protostadienol by helA, cytochrome P450 monooxygenases helB1-mediated and helB2-mediated oxidation at C-4 and C-16, acyltransferase helD2-dependent acetylation of 16-OH, oxidation of C-21 by cytochrome P450 monooxygenase helB4, and short chain dehydrogenase helC-dependent oxidative decarboxylation yield the fusidane skeleton (PubMed:29158519). This intermediate is further modified in three additional steps mediated by the cytochrome P450 monooxygenase helB3, the acyltransferase helD1, and the 3-ketosteroid 1-dehydrogenase helE to give helvolic acid (PubMed:19415934, PubMed:19216560, PubMed:29158519). Compared with the late stages in the biosynthesis of helvolic acid, enzymes involved in the early stage modifications act in a relatively strict order (PubMed:29158519). The hydroxylation of C-16 by helB1 and subsequent acetylation by helD2 should occur before the helB3-mediated oxidation of C-21 (PubMed:29158519). C-4 demethylation in fusidane-type antibiotics proceeds in an unusual manner though it is also achieved by oxidative decarboxylation (PubMed:19415934, PubMed:29158519). The methyl group at C-4 beta position is oxidized by helB1 and subsequently removed by the short chain dehydrogenase helC (PubMed:19415934, PubMed:29158519).
Sequence
MATDSSMPGTVIGKAEFSDTKAASEFGTDLSRWRLNVDNGRHMWEYLESEDEARKRPQSFLEKYWLGLPYELPARPRATCALEAVENGWEFFKRLQTADGHWGCNDDGPLFVTSGMVIARYIVGIPIDSHMKQEMCRYLLNVVNEDGGWGLFIQSPSTVFGTVMNYCMLRILGLGPEHPAMAKARNTLHRLGSARATPTWGKFWLCVLGVYEWEGMVPLPPEPLLVPASLPFNPGKWWVHTRNVYISMSYLYGHRFSMPPNKLVQALRDELYDIPYQQINWPAQRTNVSAADRLTDPTWIQRSFTSALTMYETFKIPFLRRRALNEALFQIETETRNTHYLCIAPVSFASNMLALYHAHGRDSHWIRGMRDRFIDPMWLCREGLAASGTNGTSLWDTALTVQATIDAGLAARPENQAILRKALEFIDNSQIREDPLGVHHVYRQPTRGAWPFSTRDQSYAVSDTTAEAVKVIVLLQRIEGFPSRISDERLQQAIDLILGMENAGGGFSAYEPVRGPKFLELLNITELYENVMTDNLYPECTSSVIMCLTTFAREYPTYRPRDIQACLSRSIDYLLRSQYPNGGWFASWGVCFTYATMFALQGLACMGWNESNCAACQRACSFLLQHQNPDGGWGESLDTVRFKQYLPHPDGSQVTNTAYAVIGLLAARCGNHEAIRRGVAYLVKEQQDTGEWLPGPLEGVFAPPGGMRYPNYKFHFTLMALGRYVAIHGNECLAI