A REGULATORY MECHANISM FOR THE BALANCED SYNTHESIS OF MEMBRANE PHOSPHOLIPID SPECIES IN ESCHERICHIA-COLI

The mechanism that assures the balanced synthesis of zwitterionic (pho sphatidylethanolamine) and acidic phospholipids (phosphatidylglycerol and cardiolipin) in Escherichia coli has been examined by genetically manipulating the two enzymes at the biosynthetic branch point, i.e., p hosphatidylglycerophosphate synthase, encoded by pgsA, and phosphatidy lserine synthase, encoded by pssA. A mutant in which the most part of the pssA gene was replaced with a drug resistance gene lacked phosphat idylserine synthase and phosphatidylethanolamine and required divalent metal ions for growth, as did a previously reported insertion-inactiv ated pssA mutant. When this mutant harbored a plasmid containing a Bac illus subtilis gene that encodes membrane-bound phosphatidylserine syn thase, the phosphatidylethanolamine content was dependent on its activ ity, in contrast to that with the soluble E. coli counterpart. A defec tive mutation, pgsA3, caused reductions not only in acidic-phospholipi d synthesis but also in phosphatidylethanolamine synthesis, despite th e normal level of phosphatidylserine synthase activity. These results, together with previous observations, indicate that phosphatidylserine synthesis requires the membrane-associated form of phosphatidylserine synthase, which is related to the membrane-levels of acidic phospholi pids, thus yielding balanced compositions of zwitterionic and acidic p hospholipids.