Structure and function of an ancestral acetyl-CoA carboxylase
EMSL Project ID
51601
Abstract
Acetyl-CoA carboxylase (ACC) is a biotin-dependent enzyme that catalyzes the first committed step in lipid biosynthesis in Bacteria and Eukarya. We aim to characterize AccM, an ACC from an oleaginous actinobacteria. We are pursuing the cryo-electron microscopy structure of the ~400 kDa dimeric AccM of Rhodococcus jostii RHA1, a multidomain structure conserved with eukaryotic ACCs: an N-terminal biotin carboxylase (BC), a biotin carboxyl carrier protein (BCCP), a central domain (CD), and a C-terminal carboxyl transferase (CT). Similar to eukaryotic ACCs, AccM catalyzed the carboxylation of short-chain acyl-CoAs, with highest specificity for acetyl-CoA, and was subject to product inhibition and potent feedback inhibition. Deletion of accM reduced both TAG accumulation and the acyl-chain length of cellular fatty acids in Rhodococcus, predominantly affecting the neutral lipids pool, suggesting that AccM primarily provides malonyl-CoA for triacylglycerol biosynthesis. Finally, phylogenetic analyses suggested that AccM arose within an actinobacterial ancestor and suggested an ancient transfer of AccM gave rise to eukaryotic ACCs. This further suggests an intriguing role for Actinobacteria in eukaryogenesis and the evolution of fatty acid biosynthesis in eukaryotes.
Project Details
Start Date
2020-08-15
End Date
2020-11-15
Status
Closed
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Principal Investigator
Team Members