RT Journal Article
SR Electronic
T1 Evolution of chalcone isomerase from a non-catalytic ancestor
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 174128
DO 10.1101/174128
A1 Miriam Kaltenbach
A1 Jason R. Burke
A1 Mirco Dindo
A1 Anna Pabis
A1 Fabian S. Munsberg
A1 Avigayel Rabin
A1 Shina C. L. Kamerlin
A1 Joseph P. Noel
A1 Dan S. Tawfik
YR 2017
UL http://biorxiv.org/content/early/2017/08/10/174128.abstract
AB The emergence of catalysis in a non-catalytic protein scaffold is a rare, unexplored event. Chalcone isomerase (CHI), a key enzyme in plant flavonoid biosynthesis, is presumed to have evolved from a non-enzymatic ancestor related to the widely-distributed fatty-acid binding proteins (FAPs) and a plant protein family with no isomerase activity (CHILs for “CHI-like”). Ancestral inference confirmed that CHI evolved from a protein lacking isomerase activity. We also 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 can readily emerge despite a catalytically inactive starting point. X-ray crystallography, NMR, and MD 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.