Unexpected assembly machinery for 4(3H)-quinazolinone scaffold synthesis.

ABSTRACT: 4(3H)-quinazolinone is the core scaffold in more than 200 natural alkaloids and numerous drugs. Many chemosynthetic methodologies have been developed to generate it; however, investigation of its native enzymatic formation mechanism in fungi has been largely limited to fumiquinazolines, where the two nitrogen atoms come from anthranilate (N-1) and the α-NH₂ of amino acids (N-3). Here, via biochemical investigation of the chrysogine pathway, unexpected assembly machinery for 4(3H)-quinazolinone is unveiled, which involves a fungal two-module nonribosomal peptide synthase ftChyA with an unusual terminal condensation domain catalysing tripeptide formation; reveals that N-3 originates from the inorganic ammonium ions or the amide of L-Gln; demonstrates an unusual α-ketoglutarate-dep

SUBMITTER: Chen XW 

PROVIDER: S-EPMC9622831 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature