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Two-Enzyme Pathway Links l-Arginine to Nitric Oxide in N-Nitroso Biosynthesis

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    Two-Enzyme Pathway Links l-Arginine to Nitric Oxide in N-Nitroso Biosynthesis
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    Cite this: J. Am. Chem. Soc. 2019, 141, 9, 4026–4033
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    https://doi.org/10.1021/jacs.8b13049
    Published February 14, 2019
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    Abstract

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    Nitric oxide (NO) has wide-ranging roles in biology, but less is known about its role in building chemical diversity. Here we report a new route to NO from the biosynthetic pathway to the N-nitroso compound streptozocin. We show that the N-nitroso group of streptozocin comes from the biosynthetic reassembly of l-arginine, with the guanidino nitrogens forming a nitrogen–nitrogen bond. To understand this biosynthetic process, we identify the biosynthetic gene cluster of streptozocin and demonstrate that free l-arginine is N-methylated by StzE to give Nω-monomethyl-l-arginine. We show that this product is then oxidized by StzF, a nonheme iron-dependent enzyme unrelated to known nitric oxide synthases, generating a urea compound and NO. Our work implies that formation and capture of NO is the likely route to N-nitroso formation in vivo. Altogether, our work unveils a new enzyme pair for the production of NO from l-arginine and sets the stage for understanding biosynthetic routes to N-nitroso natural products.

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    Cite this: J. Am. Chem. Soc. 2019, 141, 9, 4026–4033
    Click to copy citationCitation copied!
    https://doi.org/10.1021/jacs.8b13049
    Published February 14, 2019
    Copyright © 2019 American Chemical Society
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