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cctR

Gene
cctR
Protein
Cyclochlorotine biosynthesis protein R
Organism
Talaromyces islandicus
Length
261 amino acids
Function
Part of the gene cluster that mediates the biosynthesis of the mycotoxin cyclochlorotine, a hepatotoxic and carcinogenic cyclic chlorinated pentapeptide (PubMed:26954535). Cyclochlorotine is formed by the nonproteinogenic amino acids L-2-aminobutyrate (2Abu), L-beta-phenylalanine (beta-Phe), the unique L-cis-3,4-dichloroproline Pro(Cl(2)) and two L-serines (Ser) (PubMed:26954535). The condensation of the 5 building blocks is performed by the cyclochlorotine synthetase cctN, a nonribosomal peptide synthetase (PubMed:26954535). The assembled linear pentapeptide is then assumed to be released through cyclization by the terminal condensation-like domain of cctN (PubMed:26954535). Incorporation of the alternative substrates allo-threonine or alanine by the domains A3 or A1 respectively may lead to the production of the variants hydroxy-cyclochlorotine and deoxy-cyclochlorotine, respectively (PubMed:26954535). CctP probably acts as a phenylalanine aminomutase and provides the uncommon building block beta-Phe (PubMed:26954535). Furthermore, 2Abu can be synthesized from threonine by one of the threonine dehydratases and transaminases localized outside of the cluster (PubMed:26954535). The biosynthesis of the unusual dichloroproline moiety remains elusive since the actual halogenase still awaits to be detected, with the possibility that proline halogenation is accomplished by a so far unknown type of halogenase (PubMed:26954535). Finally, the cluster encoded transporters cctQ and cctS are most likely responsible for cyclochlorotine secretion and thereby may contribute to intrinsic resistance (PubMed:26954535). The functions of the remaining proteins encoded by the cluster (cctM, cctO, cctR and cctG) have not been identified yet (PubMed:26954535).
Mass
29.537 kDa
Sequence
MEEELEPLNRPTLDPDESYAEEKIYGSSHREPNSRIRVFVSLLILSNTISFGLLGWIGLSSTQASLAIPEDYAIPPRIATQYKRFWWTTEYSSKNQSQQDELWNSIVWTYGMIGVDHEWSKSQHWPDTMSLPQDKTKAVYLLQAYHEIHCLGVLRRLMSQSLAGVDFSESEHTHAHIAHCFDSLLQSTICRADSTPLYTFGGTIVGSGQQHECRDWNALRDYATQNSACYTEESGFGGQCSDGDGLVPATPMETQQDGFWL