Function
FAD-dependent monooxygenase; part of the gene cluster that mediates the biosynthesis of the indole diterpenes nodulisporic acids (NA). Nodulisporic acid A (NAA) and its chemically modified derivatives are of particular significance because of their highly potent insecticidal activity against blood-feeding arthropods and lack of observable adverse effects on mammals, in particular the tremogenicity associated with the paspaline-derived IDTs is not observed (PubMed:29283570). The geranylgeranyl diphosphate (GGPP) synthase ggs1, localized outside of the cluster, is proposed to catalyze the first step in nodulisporic acid biosynthesis via conversion of farnesyl pyrophosphate and isopentyl pyrophosphate into geranylgeranyl pyrophosphate (GGPP) (PubMed:29283570). Condensation of indole-3-glycerol phosphate with GGPP by the prenyl transferase nodC then forms 3-geranylgeranylindole (3-GGI) (PubMed:29283570). Epoxidation by the FAD-dependent monooxygenase nodM leads to a single-epoxidized-GGI that is substrate of the terpene cyclase nodB for cyclization to yield emindole SB (PubMed:29283570). The terminal methyl carbon, C28, of emindole SB is then oxidized by the cytochrome P450 monooxygenase nodW to produce nodulisporic acid F (NAF), the pentacyclic core of NAA (PubMed:29283570). NAF is converted to nodulisporic acid E (NAE) via prenylation. This step is probably performed by one of the indole diterpene prenyltransferases nodD1 or nodD2 (Probable). Several oxidation steps performed by the FAD-linked oxidoreductase nodO and one of the cytochrome P450 monooxygenase nodR, nodX or nodZ further convert NAE to nodulisporic acid D (NAD) (Probable). NAD is substrate of cytochrome P450 monooxygenase nodJ to produce the precursor of nodulisporic acid C (NAC), converted to NAC by one of the indole diterpene prenyltransferases nodD1 or nodD2 (Probable). The FAD-dependent monooxygenase nodY2 then oxidizes NAC to nodulisporic acid B (NAB) (Probable). Finally NAB is converted to NAA by one of the cytochrome P450 monooxygenases nodR, nodX or nodZ (Probable).
Sequence
MSTPEFKVIIVGGSLAGLTLAHCLLRAGISHIVLERRSVIAPEEGASIGILPNGARVLDQLGIYEHIQDTTEPLSTAHIRYPDGFYFSSRYPEIIKERFGYPIAFLPRRRLLEILYTSYPDHSNIYTNKNVIKVQSHDNQVSVLTEDGNTYRGDLVVGADGVNSRVLSEIWKLAGNPSLTKREGRGRTIEYACVFGISSPISDLKPGEQVNAFYDGLTIVTIHGRNGEIFWFFIKKLSRRYIYPDLIRLQQKDAEGICEEAKSLTVWKGVTFGDIWERRETASLTVLDEFLHHTWSWDRSVCVGDSIHKMTPNFGQGANTAIEDSAALANLLHSLIKEKRAEKPTDSDISLLLRQFKSQRLRRVQKIYKMSRFVTRLQARDGLLNTLLGRHYAPYAADLPAKIASGCIAGAEVLDYLPLPKVTGAGWNRGHRRSTMYILLGFTGVFTSALAMVVLLHIRDIAS