Skip to main content
eScholarship
Open Access Publications from the University of California

Investigating molecular interactions in modified acyl carrier proteins

  • Author(s): Haushalter, Robert William
  • et al.
Abstract

Understanding molecular interactions that govern how fatty acids and polyketides are made will be crucial to engineering these metabolic pathways towards important clinical and industrial goals. The work outlined in this thesis aims to answer questions that remain about how acyl carrier proteins interact with bound acyl groups and with catalytic domains in these important metabolic pathways. The interdisciplinary approach to investigating ACP interactions in this work focuses on functionalizing ACP domains with synthetic molecules that mimic biological substrates, and then performing structural studies on these functionalized ACPs with protein NMR. The data presented sheds light on interaction sites on ACP that promote the release and delivery of bound substrates. We demonstrate the ability to crosslink ACP to cognate enzyme domains and prepare NMR samples of these crosslinked species that are suitable for structural analysis. Finally, we show that ACPs from type II polyketide synthases interact with polar, cyclic substrate analogs appended via 4'phosphopantetheine linkage. The methods outlined here will be used to understand the molecular basis for the dynamic associations of ACPs in fatty acid and polyketide synthases

Main Content
Current View