Mechanistic determinants of fatty acid chain length in fatty acid synthase: The case of dairy fat

Lipid chemical and structural properties are responsible for the technological, health and rheological properties of dairy products. Inability to properly mimic those compositional properties will result in lower product quality as well as lower public acceptance. These properties stem from a unique composition of dairy fatty acids which are enriched with short- and medium-chain fatty acids with a carbon chain length of up to 14 atoms, a trait shared among dairy ruminants such as bovine, caprine and ovine, but different from most non-ruminant species. These fatty acids are produced in the mammary gland epithelial cells, by the fatty acid synthase (FASN) multienzyme. While de novo synthesis of fatty acids is highly conserved throughout evolution, and the same sequential elongation and condensation of acetyl-CoA and malonyl-CoA units follow the same mechanistic steps, still the products vary between organisms and tissues. Here we address the fundamental question of ruminant dairy fat production and discuss the general and specific properties of mammalian and ruminant FASN and their potential contribution to the production of short- and medium-chain fatty acids in ruminant milk fat. Current knowledge regarding each catalytic activity of the FASN multi-enzyme is reviewed with special emphasis on consequences to fatty acid profile produced by ruminant FASN. To identify ruminant specific FASN properties with potential to attribute to dairy fat composition, FASN protein sequence was analyzed and compared among 13 ruminant and non-ruminant mammalian species. Unravelling these distinctive properties will expand our understanding of this fundamental question in lipid metabolism and shed light on the evolution of the high diversity of mammalian milk, and specifically on dairy ruminant milk fat.