Belactosins
and hormaomycins are peptide natural products containing
3-(2-aminocyclopropyl)alanine and 3-(2-nitrocyclopropyl)alanine
residues, respectively, with opposite stereoconfigurations of the
cyclopropane ring. Herein we demonstrate that the heme oxygenase-like
enzymes BelK and HrmI catalyze the N-oxygenation of l-lysine
to generate 6-nitronorleucine. The nonheme iron enzymes BelL and HrmJ
then cyclize the nitroalkane moiety to the nitrocyclopropane ring
with the desired stereochemistry found in the corresponding natural
products. We also show that both cyclopropanases remove the 4-proS-H of 6-nitronorleucine during the cyclization, establishing
the inversion and retention of the configuration at C4 during the
BelL and HrmJ reactions, respectively. This study reveals the unique
strategy for stereocontrolled cyclopropane synthesis in nature.
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