Benzoxazoles are heterocyclic ring structures, which occur in various commercially available drugs, such as the transthyretin amyloidosis medicine tafamidis or the non‑steroidal antiinflammatory drug flunoxaprofen.[1,2] In recent years, several benzoxazole natural products with promising bioactivities have been discovered.[3] The identification of their biosynthetic gene clusters revealed the requirement of AMP ligases and condensing amidohydrolases for benzoxazole production. AMP ligases activate an aromatic carboxylic acid and ligate it to another carboxylic acid, while the amidohydrolase is in charge of condensing the ligation product into a benzoxazole.[4] Most of the reported benzoxazoles are produced by actinomycetes, such as the antibiotic caboxamycin from Streptomyces sp. NTK 937 and the antineoplastic agent nataxazole from Streptomyces sp. Tü 6176.[5,6] Upon a homology-based sequence search, potential benzoxazole biosynthetic gene clusters in various myxobacteria were identified. Among others, we found a biosynthetic gene cluster in Pyxidicoccus fallax, which we analysed further. For this, we heterologously expressed the detected biosynthesis genes in E. coli and performed in vitro assays with the gene products, which confirmed their ability to produce benzoxazoles. The results of these assays, along with the structures of the produced benzoxazoles, will be presented in this poster.
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