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atnF

Gene
atnF
Protein
Fatty acid synthase subunit alpha
Organism
Emericella nidulans (strain FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139)
Length
1659 amino acids
Function
Fatty acid synthase subunit alpha; part of the gene cluster that mediates the biosynthesis of aspercryptins, linear lipopeptides built from six amino acids including 2 highly unusual and nonproteogenic amino acids, 2-amino-octanoic acid (2aoa) and 2-amino-dodecanol (2adol) (PubMed:23248299, PubMed:27310134, PubMed:26563584). The core structure of aspercryptins is as follows: Ser/Ala-Thr-Ile/Val-2aoa-Asn-2adol (PubMed:27310134). The first step of aspercryptin biosynthesis is the generation of the fatty acid precursors, octanoic and dodecanoic acids, by the FAS subunits atnF and atnM (PubMed:27310134, PubMed:26563584). The fatty acid precursors are likely transformed into the corresponding alpha-amino fatty acids in three steps (PubMed:27310134, PubMed:26563584). First, they are hydroxylated by the cytochrome P450 monooxygenase atnE, then oxidized to the corresponding alpha-keto acids by the NAD(P)-dependent oxidoreductase atnD, and finally converted to the alpha-amino fatty acids by the PLP-dependent aminotransferases atnH or atnJ (PubMed:27310134, PubMed:26563584). the alpha-amino fatty acids, 2-amino-octanoic and 2-amino-dodecanoic acids, are recognized, activated, and covalently tethered to the NRPS atnA by its fourth and sixth adenylation domains (PubMed:27310134). The second module of atnA is the Thr module and contains an epimerase (E) domain responsible for the epimerization of Thr to D-allo-Thr (PubMed:26563584). Additionally, despite atnA having only one epimerase domain, the first amino acid of aspercryptin A1 is D-Ser, suggesting that serine is either loaded directly as D-Ser on the first module or that the epimerase domain in the threonine module epimerizes both L-Ser and L-Thr (PubMed:27310134). After condensation of the hexapeptide of aspercryptin, the C-terminal reductase (TE) domain might be involved in the reductive release and production of the aldehyde hexapeptide (PubMed:26563584). Further reduction would generate aspercryptins (PubMed:27310134, PubMed:26563584). The variety of aspercryptins produced reflects the flexibiliy of the atnA NRPS, allowing incorporation of alanine instead of serine, valine for isoleucine, and a C10 fatty amino alcohol instead of the C12 version (PubMed:27310134). AtnB seems to be involved in the selectivity for Ile versus Val by the third module (PubMed:26563584). Moreover, type B, C and D aspercryptins have an additional N-terminal cichorine, acetyl and propionyl group respectively (PubMed:27310134).
Similarity
Belongs to the thiolase-like superfamily. Fungal fatty acid synthetase subunit alpha family.
Mass
181.995 kDa
Sequence
MVAAQDDGAQRKLAHTLLLELMSYQFASPVRWIETQDVVLGQYRAERIIEIGPAATLTNMIKQTVQSKFLHSDRASLLQRQLLASEKQGKDIYYEDDGVGIGTGAEAPAPSAKTQAQASGGAGTIAGAGSSTAPVTAPPAPAAAKAVPAGGMQAIEDRQAQAFEIVRTLLSRILKIALTDVVGTQSIKSLSGGRSTLENEIIGDLASEFGSLPDRAEDLTVNDLSAALQKTFTGQMRKVILKMLHAMFASKMPGQFTVATARTYLHSRWGLGSGRQDSVLLLAIAQQPGSRLKEEAEARSFFDGLVQFYADEHGLTLGANSGAADETSGLGGGLVMDQKTLAALTGGQQELSKALLKIYAKHLDIDLDGDRRALHDLQATVEKDLRLALDQIHQELGEDFTDGVQPVFSARKARRFDSAWSWALQDLLQLYYEVSRTGGETEVDLAAKRCKHIEDAADPRLLDVLQRIVGRFEQQPVLSSMFTQLAQRCRDSLLHGPRYLARPDQQGPRTTISAEGDITYTEQERAEPVPLADLVYLPKSTEAAPLEPFLHLKQRTGGSSAWTYSHDLTEQYRAVLEQATTVGESFAGRSVLITGAGVGSIGAEVLKGLLAGGARVIVTTSRFSSSVVRKYQDLYTQVGSRGSELVVVPFNQASVQDVTALVNYIYDAQGGLHWDLDHILPFAAMPENGRTIEKIDPHSELAHRTMMVNTLRLLGAVKARKEAQGSRTRPTQVILPLSPNHGVFGGDGLYSESKLGLEALFNRWHSEDWSDYLSVCGAVIGWTRGTGLMSGNNLVAEGIEELGCRTFSQQEMAQCLLCLMFNTMCSLCEEAPLYADLSGRMGAVQNLRQKVQELRTEINETANTRRALLEELAMEARCSEGPTPTIDSEPAKATATPTLTAHVRLDFPPTVDYNQEIKPLTADLQGMVDLDRVVVVTGFGEIGPWGNARTRWEMEAYGEFSLEGCVEMAWLMGLIRYENSSSPGWVDAKTNERVHDHEVKHKYEEHILSHTGIRLIEPDRFGANYHPEHKQLLHEVLIQEDFPELEVPEATAQQMKLEHGNKVDIIPDPEGGDQCRVVLKKGAKLMVPKALRLDRMVIGQIPTGWDARKYGIPEDVISQVDPVTLYMLACSIEALLSSGITDPYEIYRYIHVSEAGNCVGSSLGGFNSLQQMYRGRYMEKEVQKDILQETFVNTIGAWMNMLLMSSAGPIRTPVGACATAIESVELGYDTLISGKAKFCFVGGGDDFGEEVLYEFANMKATANTVDEFEQGREASEMSRPAASTRNGFMESHGCGVQILTTARLAIEMGLPVRGVIAFVETSSDKASRSVPAPGRGILSKAREVRSSSPSSSLISSPLLNISNRRKRLDFRKKQIEFARETALEELQLEIAHVEESEVEDYIRERTAQINAEAQKDLRNAQYHLGNAFWQNDPSIAPLRGALAVWGLTIDDLDVASFHGTSTKLNEKNECSLIQAQLSHLGRAKGNVILGVFQKYLTGHPKGAAGAWMLNGALQILDTGIVPGNRNLDNVEAELQKNEQIAFLNRSLDTGRGSMRAVSVTSFGFGQKGAQTIVVHPKYLFATLEEQEYEEYLDKRAKRQKKADSFFYRGLASNRLFELKTAPPWAPQKELETLLDPTPPQTNVDDRVARSIVQQESAEP