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Abstract

Fatty acid (FA) biosynthesis plays a central role in the metabolism of
living cells as building blocks of biological membranes, energy reserves of the cell,
and precursors to second messenger molecules. In keeping with its central metabolic
role, FA biosynthesis impacts several cellular functions and its misfunction is linked
to disease, such as cancer, obesity, and non-alcoholic fatty liver disease. Cellular FA
biosynthesis is conducted by fatty acid synthases (FAS). All FAS enzymes catalyze
similar biosynthetic reactions, but the functional architectures adopted by these
cellular catalysts can differ substantially. This variability in FAS structure amongst
various organisms and the essential role played by FA biosynthetic pathways makes
this metabolic route a valuable target for the development of antibiotics. Beyond
cellular FA biosynthesis, the quest for renewable energy sources has piqued interest
in FA biosynthetic pathway engineering to generate biofuels and fatty acid derived
chemicals. For these applications, based on FA biosynthetic pathways, to succeed,
detailed metabolic, functional and structural insights into FAS are required, along
with an intimate knowledge into the regulation of FAS. In this review, we summarize
our present knowledge about the functional, structural, and regulatory aspects
of FAS.