Acyl carrier protein explained

The acyl carrier protein (ACP) is a cofactor of both fatty acid and polyketide biosynthesis machinery. It is one of the most abundant proteins in cells of E. coli.^[1] In both cases, the growing chain is bound to the ACP via a thioester derived from the distal thiol of a 4'-phosphopantetheine moiety.

Structure

The ACPs are small negatively charged α-helical bundle proteins with a high degree of structural and amino acid similarity. The structures of a number of acyl carrier proteins have been solved using various NMR and crystallography techniques. The ACPs are related in structure and mechanism to the peptidyl carrier proteins (PCP) from nonribosomal peptide synthases.^{[2] [3] [4] [5]}

Biosynthesis

Subsequent to the expression of the inactive apo ACP, the 4'-phosphopantetheine moiety is attached to a serine residue. This coupling is mediated by acyl carrier protein synthase (ACPS), a 4'-phosphopantetheinyl transferase. 4'-Phosphopantetheine is a prosthetic group of several acyl carrier proteins including the acyl carrier proteins (ACP) of fatty acid synthases, ACPs of polyketide synthases, the peptidyl carrier proteins (PCP), as well as aryl carrier proteins (ArCP) of nonribosomal peptide synthetases (NRPS).

Notes and References

1. 10.1042/BJ20140239. The Chain-Flipping Mechanism of ACP (Acyl Carrier Protein)-Dependent enzymes Appears Universal. 2014. Cronan. John E.. Biochemical Journal. 460. 2. 157–163. 24825445.
2. Roujeinikova A, Baldock C, Simon WJ, Gilroy J, Baker PJ, Stuitje AR, Rice DW, Slabas AR, Rafferty JB . X-ray crystallographic studies on butyryl-ACP reveal flexibility of the structure around a putative acyl chain binding site . Structure . London, England. 10 . 6 . 825–35 . June 2002 . 12057197 . 10.1016/s0969-2126(02)00775-x . free .
3. Crawford JM, Vagstad AL, Ehrlich KC, Udwary DW, Townsend CA . Acyl-carrier protein-phosphopantetheinyltransferase partnerships in fungal fatty acid synthases . ChemBioChem . 9 . 10 . 1559–63 . July 2008 . 18551496 . 3189688 . 10.1002/cbic.200700659 .
4. Volkman BF, Zhang Q, Debabov DV, Rivera E, Kresheck GC, Neuhaus FC . Biosynthesis of D-alanyl-lipoteichoic acid: the tertiary structure of apo-D-alanyl carrier protein . Biochemistry . 40 . 27 . 7964–72 . July 2001 . 10.1021/bi010355a . 11434765 .
5. Weber T, Baumgartner R, Renner C, Marahiel MA, Holak TA . Solution structure of PCP, a prototype for the peptidyl carrier domains of modular peptide synthetases . Structure . 8 . 4 . 407–18 . April 2000 . 10801488 . 10.1016/s0969-2126(00)00120-9 . free .