The vertebrate fatty acid synthase is a large homodimeric, m…
The vertebrate fatty acid synthase is a large homodimeric, multifunctional enzyme consisting of two polypeptides, each containing a series of catalytic domains located along the linear primary structure, as depicted in the figure below (a schematic of a single polypeptide is shown; each domain is depicted as a rectangle on the linear polypeptide). Polyketides (PK) and nonribosomal polypeptides (NRP) are two molecular families of natural products biosynthesized by many plants, bacteria, and fungi. Polyketides and nonribosomal peptides have received considerable attention because they typically demonstrate antimicrobial activity, making them attractive molecules for the development of novel antibiotics. The type I polyketide synthases are analogous to the vertebrate fatty acid synthases, in both the organization (topology) of the protein’s primary sequence and in terms of the catalytic mechanism/chemistries. A phosphopantetheinyl transferase (Ppan transferase) is required to activate a fatty acid synthase, polyketide synthase, and nonribosomal peptide synthase, by attachment of a phosphopantetheine prosthetic group. The following are excerpts from a fairly recent publication: In enzymes such as fatty acid synthases, polyketide synthases, and nonribosomal peptide synthases, acyl groups (see below) are tethered to the phosphopantetheine arm’s sulfhydryl moiety via what type of linkage?