Cofactors

There are no Cofactors for this Enzyme

Reaction Mechanism

malonyl-CoA-acyl carrier protein transacylase By Reference

In Escherichia coli Fatty acid synthesis, FAS II includes a specific malonyl-CoA:ACP transacylase (MCAT), which catalyses specifically the elongation step. The initiation of each elongation step in the fatty acid synthesis cycle requires the transfer of a malonyl moiety from the respective CoA thioester to the -SH group of the phosphopantetheine arm of the acyl carrier protein (ACP), the central component of any FAS. MCAT, along with Acyl-carrier-protein S-acetyltransferase (EC 2.3.1.38), is essential for the initiation of fatty-acid biosynthesis in bacteria. This enzyme also provides the malonyl groups for polyketide biosynthesis.




• Summary
• Step 1
• Step 2
• Step 3
• Step 4
• Step 5
• Products

The catalytic residues consist of a conventional Ser-His dyad, which is unusually hydrogen to the main chain carbonyl of a glutamine residue. The reactions consists of an acylation step and the subsequent transfer of the acyl moiety proceed via tetrahedral intermediates, analogously to serine proteases. His201 deprotonates Ser92 to form a nucleophile. This subsequently attacks the carbonyl group-subsequent break down of this tetrahedral intermediate eliminates CoA forming a thioester with the enzyme. His201 then deprotonates a water molecule, which nucleophilically attacks the carbonyl group a second time break down results in elimination of the enzyme.

Catalytic Residues

AA	Uniprot	Uniprot Resid	PDB	PDB Resid
Leu	P0AAI9	93	1mla	93
Ser	P0AAI9	92	1mla	92
His	P0AAI9	201	1mla	201
Arg	P0AAI9	117	1mla	117
Gln	P0AAI9	11	1mla	11
Gln	P0AAI9	250	1mla	250

Step Components

intermediate formation, enzyme-substrate complex formation, bimolecular nucleophilic addition, proton transfer, native state of enzyme regenerated, enzyme-substrate complex cleavage, overall reactant used, unimolecular elimination by the conjugate base, bimolecular nucleophilic substitution, intermediate collapse, overall product formed



Step 1.

Ser92 is activated towards nucleophilic attack at the thio-carbonyl of malonyl-CoA by the general base His201. A catalytic dyad is present between Ser92A and His201A, with the protonated form of His201A being stabilised through a hydrogen bond with the main chain carbonyl of Gln250A [PMID:7768883].



Step 2.

The tetrahedral enzyme-substrate intermediate collapses, eliminating the coenzyme A component.



Step 3.

The terminal thiolate of the previously eliminated CoA acts as a general base towards His201.



Step 4.

The enzyme-malonyl carbonyl linkage acts as an electrophile towards the terminal thiol of the acyl carrier protein which is deprotonated by the general acid His201.



Step 5.

The tetrahedral intermediate collapses eliminating the malonyl acyl-carrier protein adduct and free serine side chain, which is reprotonated by the general acid His201A.



Products.

The products of the reaction.

View Reaction Mechanisms in M-CSA

Reaction Parameters

• Kinetic Parameters

  Organism	KM Value [mM]	Substrate	Comment
  Plasmodium falciparum	0.0092	malonyl-CoA	acyl carrier protein mutant T65A, pH 7.5, 25°C
  Escherichia coli	0.0095	malonyl-CoA	wild-type acyl carrier protein, pH 7.5, 25°C

• Temperature

  There are no reaction parameters information for this Enzyme.

• pH

  Organism	pH Range	Comment
  Escherichia coli	5 - 10	about half-maximal activity at pH 5.0, about 80% of maximal activity at pH 10.0
  Persea americana	6.2 - 9.8	about half-maximal activity at pH 6.2, about 65% of maximal activity at pH 9.8
  Glycine max	7.5 - 8.5	maximal activity

Associated Proteins

Citations

• Computationally Guided Enzymatic Studies on Schizochytrium-Sourced Malonyl-CoA:ACP Transacylase.
• Integrative transcriptome and proteome revealed high-yielding mechanisms of epsilon-poly-L-lysine by Streptomyces albulus.
• Linum usitatissimum AccD Enhances Seed Fatty Acid Accumulation and Tolerance to Environmental Stresses during Seed Germination in Arabidopsis thaliana.
• Enhanced production of iturin A by strengthening fatty acid synthesis modules in Bacillus amyloliquefaciens.
• Whole-genome sequencing-based characterization of Streptomyces sp. 6(4): focus on natural product.
• Proteogenomic analysis of Serratia marcescens using computational subtractive genomics approach.
• Recessive pathogenic variants in MCAT cause combined oxidative phosphorylation deficiency.
• Transcriptomic, Physiological, and Metabolomic Response of an Alpine Plant, Rhododendron delavayi, to Waterlogging Stress and Post-Waterlogging Recovery.
• Global transcriptomic analysis reveals candidate genes associated with different phosphorus acquisition strategies among soybean varieties.
• Biochemical Process and Microbial Evolution in the Conversion of Corn Straw Combined with Coal to Biogas.
• Metabolic and transcriptomic study of pennycress natural variation identifies targets for oil improvement.