The chloroalkaloid (\u2212)-acutumine is biosynthesized via a Fe(II)- and 2-oxoglutarate-dependent halogenase in Menispermaceae plants

Colin Y Kim,Fu-Shuang Li,Jing-Ke Weng,Tomáš Pluskal,Christopher M Glinkerman,Andrew J Mitchell

doi:10.1038/s41467-020-15777-w

Abstract

Plant halogenated natural products are rare and harbor various interesting bioactivities, yet the biochemical basis for the involved halogenation chemistry is unknown. While a handful of Fe(II)- and 2-oxoglutarate-dependent halogenases (2ODHs) have been found to catalyze regioselective halogenation of unactivated C–H bonds in bacteria, they remain uncharacterized in the plant kingdom. Here, we report the discovery of dechloroacutumine halogenase (DAH) from Menispermaceae plants known to produce the tetracyclic chloroalkaloid (−)-acutumine. DAH is a 2ODH of plant origin and catalyzes the terminal chlorination step in the biosynthesis of (−)-acutumine. Phylogenetic analyses reveal that DAH evolved independently in Menispermaceae plants and in bacteria, illustrating an exemplary case of parallel evolution in specialized metabolism across domains of life. We show that at the presence of azide anion, DAH also exhibits promiscuous azidation activity against dechloroacutumine. This study opens avenues for expanding plant chemodiversity through halogenation and azidation biochemistry.

Highlights

Plant halogenated natural products are rare and harbor various interesting bioactivities, yet the biochemical basis for the involved halogenation chemistry is unknown
While maytansine was recently confirmed to be produced by endophytic bacteria[5], the synthesis of 4-chloroindole-3-acetic acid may rely on symbiotic bacterial metabolism, as known classes of indole halogenases, which are well characterized in bacteria, are absent in sequenced legume genomes[7]
We report the discovery of dechloroacutumine halogenase (DAH) from Menispermaceae plants, an Fe(II)-dependent and 2-oxoglutarate-dependent halogenase (2ODH) that catalyzes the terminal chlorination reaction in (−)-acutumine biosynthesis

Summary

Introduction

Plant halogenated natural products are rare and harbor various interesting bioactivities, yet the biochemical basis for the involved halogenation chemistry is unknown. We report the discovery of dechloroacutumine halogenase (DAH) from Menispermaceae plants, an Fe(II)-dependent and 2-oxoglutarate-dependent halogenase (2ODH) that catalyzes the terminal chlorination reaction in (−)-acutumine biosynthesis.

Results

Conclusion