Tracing the stepwise Darwinian evolution of a plant halogenase.
Name
sciadv.adv6898.pdf
Description
Published version
Size
3.23 MB
Format
Adobe PDF
Checksum (MD5)
9b04968fa74819ad986c18aa5dba1441
Author(s)
Kim, Colin Y
Kastner, David W
Mitchell, Andrew J
Gutierrez, Michael A
Yao, Jocelyn S
Neumann, Edwin N
Kulik, Heather J
Weng, Jing-Ke
Date Issued
August 13, 2025
Journal
Science Advances
Publisher
American Association for the Advancement of Science
Citation
Colin Y. Kim et al. ,Tracing the stepwise Darwinian evolution of a plant halogenase. Sci. Adv.11, eadv 6898( 2025).
Version
Final published version
Abstract
Biohalogenation is rare in plant metabolism, with the Menispermaceae's chloroalkaloid acutumine being an exception. This involves a specialized dechloroacutumine halogenase (DAH) from the iron- and 2-oxoglutarate-dependent dioxygenase (2ODD) family. While DAH is presumed to have evolved from an ancestral 2ODD, how enzyme specialization arises through Darwinian processes remains a fundamental question in understanding metabolic evolution. Here, we investigate the evolutionary history of DAH using the chromosomal-level genome of Menispermum canadense. Phylogenomic dating and synteny analyses reveal DAH evolution through tandem duplication of an ancestral flavonol synthase (FLS) gene, followed by neofunctionalization and gene loss events. Structural modeling, molecular dynamics, and site-directed mutagenesis identify mutations enabling the catalytic switch from FLS to DAH. This required traversing a complex evolutionary landscape with deep fitness valleys separating intermediate states captured in the M. canadense genome. Our findings illustrate how enzymatic functions evolve through lineage-specific pathways, reshaping active sites and enabling catalytic mechanism-switching mutations.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Chemical Engineering
Massachusetts Institute of Technology. Department of Chemistry
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Creative Commons Attribution
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DOI of Published Version
https://doi.org/10.1126/sciadv.adv6898
