Type II fatty acid and polyketide synthases: deciphering protein-protein and protein-substrate interactions

• Published in: Natural product reports 2018-10, Vol.35 (1), p.129-145
• Main Authors: Chen, Aochiu, Re, Rebecca N, Burkart, Michael D
• Format: Article
• Language: English
• Subjects: Acyl carrier protein; Aromatic hydrocarbons; Crystallography, X-Ray; Cyclization; Fatty Acid Synthase, Type II - chemistry; Fatty Acid Synthase, Type II - genetics; Fatty Acid Synthase, Type II - metabolism; Fatty acids; Fatty-acid synthase; Helicobacter pylori - metabolism; Intermediates; Metabolites; Mutagenesis; Nuclear Magnetic Resonance, Biomolecular; Organic chemistry; Polyketide synthase; Polyketide Synthases - chemistry; Polyketide Synthases - genetics; Polyketide Synthases - metabolism; Polyunsaturated hydrocarbons; Protein interaction; Protein Interaction Maps; Proteins; Proteins - analysis; Proteins - chemistry; Proteins - genetics; Secondary metabolites; Substrate Specificity; Substrates
• ISSN: 0265-0568; 1460-4752
• DOI: 10.1039/c8np00040a

Covering: up to April 5, 2018 Metabolites from type II fatty acid synthase (FAS) and polyketide synthase (PKS) pathways differ broadly in their identities and functional roles. The former are considered primary metabolites that are linear hydrocarbon acids, while the latter are complex aromatic or polyunsaturated secondary metabolites. Though the study of bacterial FAS has benefitted from decades of biochemical and structural investigations, type II PKSs have remained less understood. Here we review the recent approaches to understanding the protein-protein and protein-substrate interactions in these pathways, with an emphasis on recent chemical biology and structural applications. New approaches to the study of FAS have highlighted the critical role of the acyl carrier protein (ACP) with regard to how it stabilizes intermediates through sequestration and selectively delivers cargo to successive enzymes within these iterative pathways, utilizing protein-protein interactions to guide and organize enzymatic timing and specificity. Recent tools that have shown promise in FAS elucidation should find new approaches to studying type II PKS systems in the coming years. Metabolites from type II fatty acid synthase (FAS) and polyketide synthase (PKS) pathways differ broadly in their identities and functional roles.