Structural insight into Pichia pastoris fatty acid synthase

• Published in: Scientific reports Vol. 11; no. 1; p. 9773
• Main Authors: Snowden, Joseph S., Alzahrani, Jehad, Sherry, Lee, Stacey, Martin, Rowlands, David J., Ranson, Neil A., Stonehouse, Nicola J.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 07.05.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 631/326/193/2543; 631/326/252/318; 631/535/1258; Biofuels; Contaminants; Cryoelectron Microscopy; Fatty Acid Synthases - chemistry; Fatty Acid Synthases - ultrastructure; Fatty acids; Fatty-acid synthase; Humanities and Social Sciences; Models, Molecular; multidisciplinary; Protein Domains; Saccharomycetales - enzymology; Science; Science (multidisciplinary); Structure-function relationships; Virus-like particles; Yeast; Yeasts
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-89196-2

Type I fatty acid synthases (FASs) are critical metabolic enzymes which are common targets for bioengineering in the production of biofuels and other products. Serendipitously, we identified FAS as a contaminant in a cryoEM dataset of virus-like particles (VLPs) purified from P. pastoris , an important model organism and common expression system used in protein production. From these data, we determined the structure of P. pastoris FAS to 3.1 Å resolution. While the overall organisation of the complex was typical of type I FASs, we identified several differences in both structural and enzymatic domains through comparison with the prototypical yeast FAS from S. cerevisiae . Using focussed classification, we were also able to resolve and model the mobile acyl-carrier protein (ACP) domain, which is key for function. Ultimately, the structure reported here will be a useful resource for further efforts to engineer yeast FAS for synthesis of alternate products.