MD Simulation of Chalcone Synthase Regulation by Chalcone Isomerase-Like Protein

Flavonoids play pivotal roles in plant growth, development, and environmental adaptation. Chalcone synthase (CHS), the first committed enzyme in the flavonoid biosynthetic pathway, directs metabolic flux from general phenylpropanoid metabolism to the flavonoid pathway. However, due to its catalytic promiscuity, CHS also produces other polyketides, which limits the synthetic efficiency of the flavonoid pathway. Although the auxiliary protein CHIL (chalcone isomerase-like protein) has been identified as a regulator of CHS enzymatic properties through physical interactions, its detailed molecular mechanism remains elusive. MD simulation results suggest that the regulatory effect of CHIL on CHS specificity likely occurs at earlier stages of the catalytic cycle, such as during substrate binding or the formation of early intermediates.