Catalysis and mechanism of malonyl transferase activity in type II fatty acid biosynthesis acyl carrier proteins.
One of the unexplored, yet important aspects of the biology of acyl carrier proteins (ACPs) is the self-acylation and malonyl transferase activities dedicated to ACPs in polyketide synthesis. Our studies demonstrate the existence of malonyl transferase activity in ACPs involved in type II fatty acid biosynthesis from Plasmodium falciparum and Escherichia coli. We also show that the catalytic malonyl transferase activity is intrinsic to an individual ACP. Mutational analysis implicates an arginine/lysine in loop II and an arginine/glutamine in helix III as the catalytic residues for transferase function. The hydrogen bonding properties of these residues appears to be indispensable for the transferase reaction. Complementation of fabD(Ts) E. coli highlights the putative physiological role of this process. Our studies thus shed light on a key aspect of ACP biology and provide insights into the mechanism involved therein.
Misra
Ashish
A
Molecular Biophysics Unit, Indian Institute of Science, Bangalore, India.
Surolia
Namita
N
Surolia
Avadhesha
A
D000213:Acyl Carrier Protein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051080:Acyl-Carrier Protein S-Malonyltransferase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000215:Acylation; D000818:Animals; D053898:Biosynthetic Pathways; D002384:Catalysis; D020134:Catalytic Domain; D004591:Electrophoresis, Polyacrylamide Gel; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism; D005227:Fatty Acids / Q000096:biosynthesis* / Q000737:chemistry; D005816:Genetic Complementation Test; D007700:Kinetics; D008314:Malonates / Q000378:metabolism*; D008958:Models, Molecular; D015394:Molecular Structure; D009154:Mutation; D010963:Plasmodium falciparum / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism
D000213:Acyl Carrier Protein; D029968:Escherichia coli Proteins; D005227:Fatty Acids; D008314:Malonates; D015800:Protozoan Proteins; D051080:Acyl-Carrier Protein S-Malonyltransferase