Fatty acid synthase <p>The yeast fatty acid synthase (FAS) is a hexameric complex (alpha 6 beta 6) of two multifunctional proteins, alpha and beta [<cite idref="PUB00008312"/>]. The alpha subunit contains two of the seven enzymatic activities required for the synthesis of fatty acids, together with the site for attachment of the prosthetic group 4'-phosphopantetheine. The beta subunit contains the remaining five enzyme domains: acetyltransferase and malonyltransferase, s-acyl fatty acid synthase thioesterase, enoyl-[acyl-carrier protein] reductase, and 3-hydroxypalmitoyl-[acyl-carrier protein] dehydratase.</p> <p> The sequential order of the five FAS1-encoded enzyme domains is co-linear in <taxon tax_id="4952">Yarrowia lipolytica</taxon> (Candida lipolytica) and <taxon tax_id="4932">Saccharomyces cerevisiae</taxon> (Baker's yeast), which observation is consistent with evidence that the functional organisation of FAS genes is similar in related organisms but differs between unrelated species [<cite idref="PUB00008313"/>].</p> <p> Sterigmatocystin (ST) and the aflatoxins (AFs) (related fungal secondary metabolites) are among the most toxic, mutagenic and carcinogenic natural products known [<cite idref="PUB00008314"/>]. In <taxon tax_id="162425">Emericella nidulans</taxon> (Aspergillus nidulans), the ST biosynthetic pathway is believed to involve at least 15 enzymatic activities; some <taxon tax_id="5067">Aspergillus parasiticus</taxon>, <taxon tax_id="5059">Aspergillus flavus</taxon> and <taxon tax_id="41061">Aspergillus nomius</taxon> strains contain additional activities that convert ST to AF. </p><p> A 60kb region of the A. nidulans genome has been characterised and found to contain virtually all of the genes needed for ST biosynthesis [<cite idref="PUB00008314"/>]. The deduced polypeptide sequences of regions within this cluster share a high degree of similarity with enzymes that have activities predicted for ST/AF biosynthesis, including a polyketide synthase, a fatty acid synthase (alpha and beta subunits), five monooxygenases, four dehydrogenases, an esterase, an 0-methyltransferase, a reductase, an oxidase and a zinc cluster DNA binding protein [<cite idref="PUB00008314"/>].</p>