Animal Fatty Acid Synthase: A Chemical Nanofactory

• Type: Another Publication in an International Scientific Journal
• Date: 2021

Authors

Paiva, P (Author) Other; Medina, FE (Author) Other; Viegas, M (Author) Other; Pedro Moradas Ferreira (Author) Other; Neves, RPP (Author) FCUP; Sousa, JPM (Author) Other; Ramos, MJ (Author) FCUP; Pedro A Fernandes (Author) FCUP

Journal

Title: Chemical Reviews

Vol. 121

Pages: 9502-9553

ISSN: 0009-2665

Publisher: American Chemical Society

Indexing

ISI Web of Knowledge - 6 Citations

Other information

Authenticus ID: P-00V-37D

DOI: 10.1021/acs.chemrev.1c00147

Abstract (EN): Fatty acids are crucial molecules for most living beings, very well spread and conserved across species. These molecules play a role in energy storage, cell membrane architecture, and cell signaling, the latter through their derivative metabolites. De novo synthesis of fatty acids is a complex chemical process that can be achieved either by a metabolic pathway built by a sequence of individual enzymes, such as in most bacteria, or by a single, large multi-enzyme, which incorporates all the chemical capabilities of the metabolic pathway, such as in animals and fungi, and in some bacteria. Here we focus on the multi-enzymes, specifically in the animal fatty acid synthase (FAS). We start by providing a historical overview of this vast field of research. We follow by describing the extraordinary architecture of animal FAS, a homodimeric multi-enzyme with seven different active sites per dimer, including a carrier protein that carries the intermediates from one active site to the next. We then delve into this multi-enzyme's detailed chemistry and critically discuss the current knowledge on the chemical mechanism of each of the steps necessary to synthesize a single fatty acid molecule with atomic detail. In line with this, we discuss the potential and achieved FAS applications in biotechnology, as biosynthetic machines, and compare them with their homologous polyketide synthases, which are also finding wide applications in the same field. Finally, we discuss some open questions on the architecture of FAS, such as their peculiar substrate-shuttling arm, and describe possible reasons for the emergence of large megasynthases during evolution, questions that have fascinated biochemists from long ago but are still far from answered and understood.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 52