Comparative genomics identified a nonribosomal peptide synthetase gene cluster (wpa), spanning two genomic scaffolds, responsible for waspergillamide A (1) in Aspergillus sp. CMB-W031. Pathway reconstitution revealed the cytochrome P450 WpaD as a gatekeeper: its presence directs biosynthesis toward the depsi-tetrapeptide diketopiperazine 2, which spontaneously dehydrates to 1 under weak acid condition, whereas its absence yields linear tetrapeptide 4. Pathway characterization further enabled structural revision of 1 and confirmed the conservation of p-nitrobenzoic acid biosynthesis in fungi.
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Zeng et al. (2025) studied this question.
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