Regulation of the E. coli phospholipid synthesis pathway

Abstract

Inside and outside, intracellular and extracellular. This distinction is vital for cells and they expend vast amounts of energy to maintain the barriers that separate the in from the out. How this barrier, the cell envelope, is constructed varies wildly between organisms. We have long exploited differences between our own membrane and the bacterial cell envelope to develop targeted antibiotics. While this has resulted in a great deal of knowledge on bacterial, and especially Escherichia coli, cell envelope biosynthesis, many aspects of its regulation are still a mystery.

The phospholipid biosynthesis pathway is one the central pathways supplying crucial building blocks (phospholipids) to both the inner and outer membranes. In E. coli, much of this pathway has been thoroughly characterized and all the enzymes have been identified. Yet, despite decades of research, how this pathway is regulated remains disputed and unclear. Recent metabolomic research on the phospholipid and the preceding fatty acid biosynthesis pathways has now identified PlsB as the central point of regulation of both pathways. Furthermore, it was shown that its regulation is post-translational, and most likely through a negative feedback loop. PlsB is the first enzyme in the phospholipid pathway and catalyzes the committed step that sees the addition of acyl-ACP to glycerol- 3-phosphate. It has long been reported that PlsB is able to self-assemble into a filament, something that in other enzymes has been shown can act as a regulatory mechanism. Combining these advances we now seek to determine if filament formation is indeed how PlsB is regulated and if, as we suspect, the abundance of the membrane, its end product, is what controls the rate of filamentation.....