Myxococcus xanthus as Host for the Production of Benzoxazoles |
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Authors: | Lea Winand Lucia Lernoud Saskia Anna Meyners Katharina Kuhr Prof. Dr. Wolf Hiller Prof. Dr. Markus Nett |
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Affiliation: | 1. Department of Biochemical and Chemical Engineering, Laboratory of Technical Biology, TU Dortmund University, Emil-Figge-Str. 66, 44227 Dortmund, Germany;2. Department of Chemistry and Chemical Biology, NMR Laboratory, TU Dortmund University, Otto-Hahn-Str. 4a, 44227 Dortmund, Germany |
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Abstract: | Benzoxazoles are important structural motifs in pharmaceutical drugs. Here, we present the heterologous production of 3-hydroxyanthranilate-derived benzoxazoles in the host bacterium Myxococcus xanthus following the expression of two genes from the nataxazole biosynthetic gene cluster of Streptomyces sp. Tü 6176. The M. xanthus expression strain achieved a benzoxazole titer of 114.6±7.4 mg L−1 upon precursor supplementation, which is superior to other bacterial production systems. Crosstalk between the heterologously expressed benzoxazole pathway and the endogenous myxochelin pathway led to the combinatorial biosynthesis of benzoxazoles featuring a 2,3-dihydroxybenzoic acid (2,3-DHBA) building block. Subsequent in vitro studies confirmed that this crosstalk is not only due to the availability of 2,3-DHBA in M. xanthus, rather, it is promoted by the adenylating enzyme MxcE from the myxochelin pathway, which contributes to the activation of aryl carboxylic acids and delivers them to benzoxazole biosynthesis. |
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Keywords: | benzoxazole combinatorial biosynthesis heterologous expression ligases Myxococcus xanthus |
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