Plasmalogen Biosynthesis by Anaerobic Bacteria: Identification of a Two-Gene Operon Responsible for Plasmalogen Production in <i>Clostridium perfringens</i>

Abstract

Plasmalogens are vinyl ether-containing lipids produced by mammals and bacteria. The aerobic biosynthetic pathway in eukaryotes and bacteria is known, but the anaerobic pathway has remained a mystery. Here, we describe a two-gene operon (plasmalogen synthase, <i>pls</i>) responsible for plasmalogen production in the anaerobic bacterium <i>Clostridium perfringens</i>. While aerobic plasmalogen biosynthesis involves an oxidative conversion of an ether to a vinyl ether, anaerobic plasmalogen biosynthesis uses the reductive conversion of an ester to an aldehyde equivalent. Heterologous expression of the <i>C. perfringens pls</i> operon in <i>E. coli</i> conferred the ability to produce plasmalogens. The <i>pls</i> operon is predicted to encode a multidomain complex similar to benzoyl-CoA reductase/hydroxylacyl-CoA dehydratase (BCR/HAD) enzymes. Versions of this operon can be found in a wide range of obligate and facultative anaerobic bacteria, including many human gut microbes.