Fatty acid synthesis and utilization in gram-positive bacteria: insights from Bacillus subtilis

The bacterial cytoplasmic membrane, consisting of roughly equal proportions of proteins and lipids, plays a crucial role in cellular growth, metabolism, and maintaining the cytoplasmic boundary. It is a dynamic, fluid matrix that separates intracellular compartments, where lipids and proteins coexist in a highly organized yet flexible arrangement. Membrane fluidity, defined as the inverse of viscosity, determines how rapidly molecules diffuse within the membrane at a given temperature. This property is vital for protein mobility and biomolecular interactions. Structurally, the membrane primarily comprises a lamellar lipid bilayer, with glycerophospholipids and fatty acids forming its core framework. In Bacillus subtilis, a key model organism for studying Gram-positive bacterial physiology, major membrane lipids include phospholipids, glycolipids, and lipoteichoic acids, the latter anchored to diacylglycerol glycolipids. This review examines the synthesis and regulation of membrane lipids in B. subtilis, with a focus on fatty acid biosynthesis, its diversification, and post-synthetic modifications such as desaturation. It also explores the production of phosphatidic acid and the integration of fatty acid and phospholipid biosynthesis. We review the well-characterized pathway of cold-induced membrane lipid modification in B. subtilis, arguably the best-studied model system for temperature sensing. This pathway is tightly linked to transcriptional responses triggered by changes in bilayer viscosity, detected by a membrane-associated thermosensor. Lastly, the review highlights the importance of fatty acid biosynthesis in B. subtilis differentiation and its contributions to the production of biotin and lipoic acid, two universal cofactors essential for fatty acid synthesis and intermediary metabolism.