Revised Manuscript Received February 28, 1989 e animal fatty acid synthase is the most sophisticated entry in the newly recognized class of multifunctional enzymes. The subunit protein of this elegant multienzyme has a molecular weight of 260000 and contains, in separate domains, seven different catalytic activities and a site for the prosthetic group, 4'-phosphopantetheine, of the acyl carrier protein. Investi-gations of fatty acid biosynthesis not only yielded information about this multienzyme system but uncovered significant concepts basic tobiochemistry at large. For instance, the notion that synthetic pathways are the reversal of degradative reactions was refuted in part by studies on fatty acid biosynthesis (Wakil et al., 1957). It is now well accepted that an-abolic pathways may not be the same as the degradative pathways. Also, the role of the vitamin biotin in biological reactions was first recognized in studies of fatty acid synthesis by the discovery of biotin as a prosthetic group of acetyl-CoA carboxylase (Wakil et al., 1958). Several such biotin-con-taining enzymes have since been recognized and studied. Moreover, the activation of acetyl-CoA carboxylase by citrate (Waite & Wakil, 1962; Martin & Vagelos, 1962) provided one of the early examples that led to the formulation of the model for allosteric modification of proteins by Monod, Wy-man, and Changeux (1965). The finding that a protein, acyl carrier protein (ACP), acts as a coenzyme was first demon-strated in enzymatic reactions involved in fatty acid synthesis (Majerus et al., 1964; Wakil et al., 1964). This protein binds substrates and all acyl intermediates as thioesters and channels them into the synthetic pathway. Finally, studies of this system (Knobling et al., 1975; Stoops et al., 1975) led to the recog-nition of multifunctional proteins as a new class of enzymes with two or more catalytic domains associated with a single polypeptide (Kirschner& Bisswanger, 1976). This multi-functional protein is encoded by a single gene which may have evolved by fusion of component genes. This review presents