asaC

Nonribosomal peptide synthetase asaC

1021 amino acids

Nonribosomal peptide synthetase; part of the gene cluster that mediates the biosynthesis of aspergillic acid, a hydroxamic acid-containing pyrazinone with aliphatic side chains that originates from leucine (Leu) and isoleucine (Ile) (PubMed:29674152). Aspergillic acid has antibiotic properties and was shown to be lethal to mice (PubMed:29674152). The first step in the pathway is the production of deoxyaspergillic acid via a condensation between the Ile amine and the Leu carboxylic acid, followed by a reductive release from the protein forming the dipeptide aldehyde NH(2)-Leu-Ile-CHO, which could undergo an intermolecular cyclization resulting in a dihydropyrazinone (PubMed:29674152). As the NRPS asaC lacks a condensation domain, it is improbable that it is responsible for condensation of Leu and Ile (PubMed:29674152). One possibility is that asaC acts on a previously condensed dipeptide and functions as a Leu-Ile reductase to yield deoxyaspergillic acid (PubMed:29674152). After asaC forms deoxyaspergillic acid, the cytochrome P450 asaD oxidizes the pyrazinone to the hydroxamic acid-containing bioactive metabolite aspergillic acid (PubMed:29674152). The hydroxylase/desaturase asaB can then convert aspergillic acid to hydroxyaspergillic acid (PubMed:29674152). Both aspergillic acid and hydroxyaspergillic acid can form complexes with iron producing ferriaspergillin analogs (PubMed:29674152).

Belongs to the NRP synthase family.

113.315 kDa

MSIFSSISSLGLEACYRHHVRTSPNATAVVDGDQSMTYRELETRVNDLASILGRENIEEEEPIGILVPMGIAHVVAQAAVLRLGGSCVPMDLSFPDQRINDLLRALKTRIVLTVESEKARFAEFQTILVDSKYANLHQNGYHEDTIPAVETGRNHRTHILHTSGTTGLPKPVEIMSKGITRMAFNTQCVEFKSTDRVAQISAPSFDAALFEIWTTLARGAAIVLLPKNVVIDPVALHDSLRKYRITSILVTTALLNHVVSAIPNAFEDLDYVLTGGEAANPSVMQVILENGPPKKLVHAYGPTECTIITTYHLTTLEEVRRGQTPIGRPLDNTTVYILDDNLQPVKEGIVGELYIGGDAVARGYLGRPEANAKSFLEVSHLSKDGSPVRIYRSGDLVRMLDTGAIEFVARADNMVKIRGFRIEPAEIEGALLKSEMVQGTVVLPVHRPGKETYIVAFVIPKHDGAFSLEQLDEYLRRRLPAYMMPRLEAVASLPLTVHGKIDRVAVMKKHMEETKRAEQQVLISSNVKDAGDSVTWLRTLWTSVLGISNIDNEASFFHLGGSSLQAAALLVHIRRRFGLTLTMQQIYDSPTLLGLASVIDAGHAKSKVDHSRLGIFIADSQLAKDIPVLSKEAPDWRSPSEGKVFLTGATGFLGTYFLRELIDRPDVRSVKCLVRASDAHSARKRLLGALDKYGLGWADNLDKVTAIAGDLGKDLFGLSETEFHELALWTSVIFHVGAHVNYVQPYEKHRNTNVYGTLNCIKLATTGRTKALHYTSTAAVTGPVSHFTGADKIPEDVDLGEFQGWLPYDIGYTQSKWVSEQLIHSMIAKGLPAIVFRPGFIMGDSLRGKGNCDDFMCRVFIGSIKLGYRPILPNQSKIMIPVDFITTALLHITSNPYNFGRTFHLVPQTPEEDTDIETSWNMLKELGYDLKAVEYKDWLEILSKDKDLLTNPLLPMLPVLQEPVRKHLTRWELYEDMATYDVTNTRRSLADRGKLKSGIGLEDLRRHVEDWVARGLVPSRN