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Two-Enzyme Pathway Links l‑Arginine to Nitric Oxide in N‑Nitroso Biosynthesis
journal contribution
posted on 2019-02-14, 00:00 authored by Hai-Yan He, Alyssa C. Henderson, Yi-Ling Du, Katherine S. RyanNitric
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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biosynthetic processbiosynthetic reassemblyl-argininebiosynthetic pathwaybiosynthetic gene clusterbuilding chemical diversityurea compoundrolenonheme iron-dependent enzymeguanidino nitrogensnitroso formationNitric Oxideunderstanding biosynthetic routesnitric oxide synthasesnitroso groupnitroso compound streptozocinenzyme pairN ω
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