10.1021/jacs.8b13049.s001
Hai-Yan He
Hai-Yan
He
Alyssa C. Henderson
Alyssa C.
Henderson
Yi-Ling Du
Yi-Ling
Du
Katherine S. Ryan
Katherine S.
Ryan
Two-Enzyme
Pathway Links l‑Arginine
to Nitric Oxide in <i>N</i>‑Nitroso Biosynthesis
American Chemical Society
2019
biosynthetic process
biosynthetic reassembly
l-arginine
biosynthetic pathway
biosynthetic gene cluster
building chemical diversity
urea compound
role
nonheme iron-dependent enzyme
guanidino nitrogens
nitroso formation
Nitric Oxide
understanding biosynthetic routes
nitric oxide synthases
nitroso group
nitroso compound streptozocin
enzyme pair
N ω
2019-02-14 00:00:00
Journal contribution
https://acs.figshare.com/articles/journal_contribution/Two-Enzyme_Pathway_Links_l_Arginine_to_Nitric_Oxide_in_i_N_i_Nitroso_Biosynthesis/7751951
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 <i>N</i>-nitroso compound streptozocin. We show that the <i>N</i>-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 <i>N</i>-methylated by StzE to give <i>N</i><sup>ω</sup>-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 <i>N</i>-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 <i>N</i>-nitroso natural products.