[19] Biosynthesis of lipoic acid and posttranslational modification with lipoic acid in Escherichia coli

This chapter presents a brief review of lipoic acid synthesis focusing on the enzymes that attach lipoic acid to the target proteins. α-lipoic acid is a cofactor covalently attached to the E2 subunits of pyruvate dehydrogenase (PDH), α-ketoglutarate dehydrogenase (KGDH) (oxoglutarate dehydrogenase), and branched-chain keto acid dehydrogenase (3-methyl-2-oxobutanoate dehydrogenase) complexes and to the glycine cleavage enzyme of Escherichia coli (E. coli)and other organisms. Attachment to such proteins is essential for the physiological function of lipoate. Lipoate is essentially an eight-carbon fatty acid modified by sulfur insertion at C-6 and C-8 to give a thiolane ring. In extracts from lplA null mutants, ligase activity is detected only when lipoyl–acyl carrier protein (lipoyl–ACP) is the lipoyl source whereas in extracts from lipB null mutants ligase activity can be detected only by use of lipoic acid plus ATP-Mg2+. However, when lplA is overexpressed from an inducible plasmid in lipB null strains, activity can be detected using lipoyl-ACP, indicating that lplA can also utilize lipoyl–ACP albeit at a reduced rate.