Isoprenoid biosynthesis in prokaryotic organisms

Abstract

Isoprenoids are ubiquitous compounds found in all living organisms. In spite of their remarkable diversity of structures and functions, all isoprenoids derive from a basic five-carbon precursor unit, isopentenyl diphosphate (IPP), and its isomer dimethylallyl diphosphate (DMAPP). Addition of IPP units to DMAPP, catalyzed by prenyltransferases, results in the synthesis of prenyl diphosphates of increasing length which are the starting points of downstream pathways leading to the synthesis of the different isoprenoid end products. For many years, it was accepted that IPP was synthesized from acetyl-CoA through the well-known mevalonate (MVA) pathway. However, an alternative MVA-independent pathway for the biosynthesis of IPP and DMAPP was identified a few years ago in bacteria, algae, and plants. This novel pathway, currently known as the methylerythritol 4-phosphate (MEP) pathway, is widely distributed in nature and is present in most eubacteria. Here, we describe the biological relevance of the main isoprenoid compounds found in prokaryotic organisms and the metabolic origin of the IPP and DMAPP used for their synthesis, with a particular emphasis on those isoprenoids present in the model bacteria Escherichia coli. Since the MEP pathway is essential in most pathogenic bacteria but is absent in animals (including humans), which synthesize isoprenoids through the MVA pathway, we also describe the recent and increasing interest of the MEP pathway enzymes as targets for the development of new antibiotics.