Cryo-EM structure of fatty acid synthase (FAS) from Rhodosporidium toruloides provides insights into the evolutionary development of fungal FAS

Protein Science : a Publication of the Protein Society
Manuel FischerMartin Grininger

Abstract

Fungal fatty acid synthases Type I (FAS I) are up to 2.7 MDa large molecular machines composed of large multifunctional polypeptides. Half of the amino acids in fungal FAS I are involved in structural elements that are responsible for scaffolding the elaborate barrel-shaped architecture and turning fungal FAS I into highly efficient de novo producers of fatty acids. Rhodosporidium toruloides is an oleaginous fungal species and renowned for its robust conversion of carbohydrates into lipids to over 70% of its dry cell weight. Here, we use cryo-EM to determine a 7.8-Å reconstruction of its FAS I that reveals unexpected features; its novel form of splitting the multifunctional polypeptide chain into the two subunits α and β, and its duplicated ACP domains. We show that the specific distribution into α and β occurs by splitting at one of many possible sites that can be accepted by fungal FAS I. While, therefore, the specific distribution in α and β chains in R. toruloides FAS I is not correlated to increased protein activities, we also show that the duplication of ACP is an evolutionary late event and argue that duplication is beneficial for the lipid overproduction phenotype.

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Citations

Nov 2, 2016·Computational and Structural Biotechnology Journal·Slavica Jonić
Feb 22, 2017·Nature Chemical Biology·Zhiwei ZhuJens Nielsen
Aug 24, 2018·Natural Product Reports·Dominik A HerbstTimm Maier
Nov 6, 2018·Protein Science : a Publication of the Protein Society·Alexander RittnerMartin Grininger
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Jul 12, 2017·Beilstein Journal of Organic Chemistry·Manuel Fischer, Martin Grininger
Mar 26, 2019·Chembiochem : a European Journal of Chemical Biology·Christina S HeilMartin Grininger
Jan 23, 2020·Scientific Reports·Manuel FischerMartin Grininger
May 31, 2020·Communications Biology·Jennifer W Lou, Mohammad T Mazhab-Jafari

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