Evolution of chalcone isomerase from a noncatalytic ancestor
Kaltenbach, Miriam ; Burke, Jason R ; Dindo, Mirco ; Pabis, Anna ; Munsberg, Fabian S ; Rabin, Avigayel ; Kamerlin, Shina C L LU
; Noel, Joseph P
and Tawfik, Dan S
(2018)
In Nature Chemical Biology
14(6).
p.548-555
- Abstract
The emergence of catalysis in a noncatalytic protein scaffold is a rare, unexplored event. Chalcone isomerase (CHI), a key enzyme in plant flavonoid biosynthesis, is presumed to have evolved from a nonenzymatic ancestor related to the widely distributed fatty-acid binding proteins (FAPs) and a plant protein family with no isomerase activity (CHILs). Ancestral inference supported the evolution of CHI from a protein lacking isomerase activity. Further, we identified four alternative founder mutations, i.e., mutations that individually instated activity, including a mutation that is not phylogenetically traceable. Despite strong epistasis in other cases of protein evolution, CHI's laboratory reconstructed mutational trajectory shows weak... (More)
The emergence of catalysis in a noncatalytic protein scaffold is a rare, unexplored event. Chalcone isomerase (CHI), a key enzyme in plant flavonoid biosynthesis, is presumed to have evolved from a nonenzymatic ancestor related to the widely distributed fatty-acid binding proteins (FAPs) and a plant protein family with no isomerase activity (CHILs). Ancestral inference supported the evolution of CHI from a protein lacking isomerase activity. Further, we identified four alternative founder mutations, i.e., mutations that individually instated activity, including a mutation that is not phylogenetically traceable. Despite strong epistasis in other cases of protein evolution, CHI's laboratory reconstructed mutational trajectory shows weak epistasis. Thus, enantioselective CHI activity could readily emerge despite a catalytically inactive starting point. Accordingly, X-ray crystallography, NMR, and molecular dynamics simulations reveal reshaping of the active site toward a productive substrate-binding mode and repositioning of the catalytic arginine that was inherited from the ancestral fatty-acid binding proteins.
(Less)
- author
- Kaltenbach, Miriam
; Burke, Jason R
; Dindo, Mirco
; Pabis, Anna
; Munsberg, Fabian S
; Rabin, Avigayel
; Kamerlin, Shina C L
LU
; Noel, Joseph P
and Tawfik, Dan S
- publishing date
- 2018-06
- type
- Contribution to journal
- publication status
- published
- keywords
- Catalysis, Catalytic Domain, Chalcones/genetics, Cloning, Molecular, Crystallography, X-Ray, Epistasis, Genetic, Escherichia coli, Evolution, Molecular, Fatty Acid-Binding Proteins/chemistry, Flavonoids/chemistry, Genes, Plant, Intramolecular Lyases/genetics, Kinetics, Magnetic Resonance Spectroscopy, Models, Molecular, Molecular Dynamics Simulation, Mutation, Phylogeny, Plant Proteins/metabolism, Plants/metabolism, Protein Conformation
- in
- Nature Chemical Biology
- volume
- 14
- issue
- 6
- pages
- 8 pages
- publisher
- Nature Publishing Group
- external identifiers
-
- scopus:85045850188
- pmid:29686356
- ISSN
- 1552-4469
- DOI
- 10.1038/s41589-018-0042-3
- language
- English
- LU publication?
- no
- id
- 6443a037-cefd-4c59-8014-f08f9c3b5087
- date added to LUP
- 2025-01-11 21:12:59
- date last changed
- 2025-06-15 16:02:58
@article{6443a037-cefd-4c59-8014-f08f9c3b5087,
abstract = {{<p>The emergence of catalysis in a noncatalytic protein scaffold is a rare, unexplored event. Chalcone isomerase (CHI), a key enzyme in plant flavonoid biosynthesis, is presumed to have evolved from a nonenzymatic ancestor related to the widely distributed fatty-acid binding proteins (FAPs) and a plant protein family with no isomerase activity (CHILs). Ancestral inference supported the evolution of CHI from a protein lacking isomerase activity. Further, we identified four alternative founder mutations, i.e., mutations that individually instated activity, including a mutation that is not phylogenetically traceable. Despite strong epistasis in other cases of protein evolution, CHI's laboratory reconstructed mutational trajectory shows weak epistasis. Thus, enantioselective CHI activity could readily emerge despite a catalytically inactive starting point. Accordingly, X-ray crystallography, NMR, and molecular dynamics simulations reveal reshaping of the active site toward a productive substrate-binding mode and repositioning of the catalytic arginine that was inherited from the ancestral fatty-acid binding proteins.</p>}},
author = {{Kaltenbach, Miriam and Burke, Jason R and Dindo, Mirco and Pabis, Anna and Munsberg, Fabian S and Rabin, Avigayel and Kamerlin, Shina C L and Noel, Joseph P and Tawfik, Dan S}},
issn = {{1552-4469}},
keywords = {{Catalysis; Catalytic Domain; Chalcones/genetics; Cloning, Molecular; Crystallography, X-Ray; Epistasis, Genetic; Escherichia coli; Evolution, Molecular; Fatty Acid-Binding Proteins/chemistry; Flavonoids/chemistry; Genes, Plant; Intramolecular Lyases/genetics; Kinetics; Magnetic Resonance Spectroscopy; Models, Molecular; Molecular Dynamics Simulation; Mutation; Phylogeny; Plant Proteins/metabolism; Plants/metabolism; Protein Conformation}},
language = {{eng}},
number = {{6}},
pages = {{548--555}},
publisher = {{Nature Publishing Group}},
series = {{Nature Chemical Biology}},
title = {{Evolution of chalcone isomerase from a noncatalytic ancestor}},
url = {{http://dx.doi.org/10.1038/s41589-018-0042-3}},
doi = {{10.1038/s41589-018-0042-3}},
volume = {{14}},
year = {{2018}},
}