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himC

Gene
himC
Protein
Cytochrome P450 monooxygenase himC
Organism
Aspergillus japonicus
Length
554 amino acids
Function
Cytochrome P450 monooxygenase; part of the him gene cluster that mediates the biosynthesis of himeic acid A, a ubiquitin-activating enzyme (E1) inhibitor (PubMed:29314577). First, himA, together with the trans-enoyl reductase himH, catalyzes the formation of apolyketide chain, which is then condensed with leucine by the NRPS activity of himA. Dieckmann cyclization and release from himA gives a tetramic acid intermediate as the product of himA PKS-NRPS (PubMed:29314577). HimG then catalyzes alpha-oxidation of the tetramic acid ring, with a subsequent rearrangement to yield apyrone intermediate (Probable). Two terminal methyl groups of polyketide and amide side chains are oxidized to carboxylic acids by himC cytochrome P450 monooxygenase to form himeic acid A (Probable). Himeic acid A is further converted to himeic acid B and C during culture growth. No gene responsible for pyrone to pyridone conversion was found in the him gene cluster and himeic acid A is non-enzymatically converted to himeic acid C by the incorporation of an ammonium nitrogen atom in a pH5 buffer, and to himeic acid B at a conversion ratio of 50% during incubation in MeOH for 5 days (PubMed:29486950).
Similarity
Belongs to the cytochrome P450 family.
Mass
62.777 kDa
Sequence
MEDIVNRLYAFDWRSLSLGSVPAPTPAPAPQSSVVHHLIAWWDQSKDSMQQYSVASVAIAGFTALVVSVALYRALFSQRQRHDPLNQGCQPLRMYPHKDRIFGLDFVYQNVTTFRRHKYLETLKNRYQTLGTTYGVRVFNRRGILTSDPENIKTILSTRFKDYSLGNRVPIMGPLLGRGIFVSDGQDWSHSRALLRPNFVKEQVADLQMIETHLAQLLKLIPSDGRTVVELQDLFLRFTLDSATDFLFGHSLHTLSRGTAKDQQFGQAFALALDDIALQFRLGPWRALRRPNKDALAAYEICRGYVEGFVADAMAYRHGKASSTGDKNTSDRSYFLKELAQATDDRDRIRDELLNILIAGRDTTASLLGSLFYVLARHPEVWQKLRSEAATQLQGAAPNYEQLRNLQYTRHCINETLRLYPPVPNNTKMAVCDTILPRGGGPKGDAPVFVPKGCTMIYTVYAMHRRTDLFGPDAEEFRPERWATQRFSWEFLPFNGGPRICLGQQYALTEAMYVLVRFAQTFQTIEAQDPAPWTEQLTLTLASNNGVKVRLKGA