Synthesis of C 5 -dicarboxylic acids from C 2 -units involving crotonyl-CoA carboxylase/reductase: The ethylmalonyl-CoA pathway

• DOI: 10.1073/pnas.0702791104
• Publication Date: 2007-06-05T01:32:29Z
• Authors: Tobias J. Erb; Ivan A. Berg; Volker Brecht; Michael Müller; Georg Fuchs; Birgit E. Alber
• Keywords: Phosphoenolpyruvate carboxylase; Rhodobacter sphaeroides; Fatty acid synthesis; Acetyl-CoA Carboxylase

Fifty years ago, Kornberg and Krebs established the glyoxylate cycle as pathway for synthesis of cell constituents from C2-units. However, since then, many bacteria have been described that do not contain isocitrate lyase, key enzyme this pathway. Here, a termed ethylmalonyl-CoA operating in such organisms is described. Isotopically labeled acetate bicarbonate were transformed to by extracts acetate-grown, lyase-negative Rhodobacter sphaeroides determined NMR spectroscopy. Crotonyl-CoA carboxylase/reductase, catalyzing crotonyl-CoA + CO2 NADPH --> ethylmalonyl-CoA- NADP+ was identified The reductive carboxylation an enoyl-thioester unique biochemical reaction, unprecedented biology. R. heterologously produced Escherichia coli characterized. carboxylase/reductase (or its gene) can be used marker presence pathway, which functions only acetyl-CoA assimilation. In Streptomyces sp., it may also supply precursors (ethylmalonyl-CoA) antibiotic biosynthesis. For methylotrophic Methylobacterium extorquens, extension serine with reactions leads simplified scheme lyase-independent C1