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.
The present study was carried out to elucidate the anti-inflammatory effect of the methanol extract obtained from the rhizomes of Zingiber cassumunar Roxb. and its active principles. The methanol extract was partitioned between ether and water, and then the ether-soluble fraction was extracted with n-hexane. The n-hexane-soluble fraction was chromatographed and part of the fraction was rechromatographed by silica gel column. Three compounds were isolated from the n-hexane-soluble fraction and the chemical structures of these compounds were identified as (E)-1-(3,4-dimethoxyphenyl)but-1-ene, (E)-1-(3,4-dimethoxyphenyl)butadiene and zerumbone. The anti-inflammatory activity of these fractions was investigated on carrageenin-induced edema in rats, as well as on acetic acid-induced vascular permeability and writhing symptoms in mice. The methanol extract (p.o.) showed both anti-inflammatory activity and analgesic activity. These activities shifted successively to ether-soluble and n-hexane-soluble fractions and to (E)-1-(3,4-dimethoxyphenyl)but-1-ene. These results suggest that the anti-inflammatory action and analgesic action of Zingiber cassumunar is the result of the (E)-1-(3,4-dimethoxyphenyl)but-1-ene that it contains.
Lolitrems are tremorgenic indole diterpenes that exhibit a unique 5/6 bicyclic system of the indole moiety. Although genetic analysis has indicated that the prenyltransferase LtmE and the cytochrome P450 LtmJ are involved in the construction of this unique structure, the detailed mechanism remains to be elucidated. Herein, we report the reconstitution of the biosynthetic pathway for lolitrems employing a recently established genome‐editing technique for the expression host Aspergillus oryzae. Heterologous expression and bioconversion of the various intermediates revealed that LtmJ catalyzes multistep oxidation to furnish the lolitrem core. We also isolated the key reaction intermediate with an epoxyalcohol moiety. This observation allowed us to establish the mechanism of radical‐induced cyclization, which was firmly supported by density functional theory calculations and a model experiment with a synthetic analogue.
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