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bioRxiv · 10.1101/365031

Glutamic acid is a carrier for hydrazine during the biosyntheses of fosfazinomycin and kinamycin

Wang, K.-K. A.·Ng, T. L.·Wang, P.·Huang, Z.·Balskus, E. P.·van der Donk, W.
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Abstract

Fosfazinomycin and kinamycin are natural products that contain nitrogen-nitrogen (N-N) bonds but that are otherwise structurally unrelated. Despite their considerable structural differences, their biosynthetic gene clusters share a set of genes predicted to facilitate N-N bond formation. In this study, we show that for both compounds, one of the nitrogen atoms in the N-N bond originates from nitrous acid. Furthermore, we show that for both compounds, an acetylhydrazine biosynthetic synthon is generated first and then funneled via a glutamyl carrier into the respective biosynthetic pathways. Therefore, unlike other pathways to NN bond-containing natural products wherein the N-N bond is formed directly on a biosynthetic intermediate, during the biosyntheses of fosfazinomycin, kinamycin, and related compounds, the N-N bond is made in an independent pathway that forms a branch of a convergent route to structurally complex natural products.

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Wang, K.-K. A., Ng, T. L., Wang, P., Huang, Z., Balskus, E. P., van der Donk, W.. 2018-07-09. Glutamic acid is a carrier for hydrazine during the biosyntheses of fosfazinomycin and kinamycin. https://doi.org/10.1101/365031

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