Long-chain fatty acid transport in bacteria and yeast. Paradigms for defining the mechanism underlying this protein-mediated process

Protein-mediated transport of exogenous long-chain fatty acids across the m embrane has been defined in a number of different systems. Central to under standing the mechanism underlying this process is the development of the ap propriate experimental systems which can be manipulated using the tools of molecular genetics. Escherichia coli and Saccharomyces cerevisiae are ideal ly suited as model systems to study this process in that both [1] exhibit s aturable long-chain fatty acid transport at low ligand concentration; [2] h ave specific membrane-bound and membrane-associated proteins that are compo nents of the transport apparatus; and [3] can be easily manipulated using t he tools of molecular genetics. In E. coli, this process requires the outer membrane-bound fatty acid transport protein FadL and the inner membrane as sociated fatty acyl CoA synthetase (FACS). FadL appears to represent a subs trate specific channel for long-chain fatty acids while FAGS activates thes e compounds to CoA thioesters thereby rendering this process unidirectional . This process requires both ATP generated from either substrate-level or o xidative phosphorylation and the proton electrochemical gradient across the inner membrane. In S. cevevisiae, the process of long-chain fatty acid tra nsport requires at least the membrane-bound protein Fat1p. Exogenously supp lied fatty acids are activated by the fatty acyl CoA synthetases Faa1p and Faa4p but unlike the case in E, coli, there is not a tight linkage between transport and activation. Studies evaluating the growth parameters in the p resence of long-chain fatty acids and long-chain fatty acid transport profi les of a fat1 Delta strain support the hypothesis that Fat1p is required fo r optimal levels of long-chain fatty acid transport.