Malonyl and Palmityl Transferase-less Mutants of the Yeast Fatty-Acid-Synthetase Complex

Abstract

146 independently isolated mutants of the fatty acid synthetase gene locus fas1 were subdivided into six different complementation groups. Three of these groups, Va, Vb and Vd, have not been described before. The mutant fatty acid synthetases isolated from representatives of complementation group Vb were specifically deficient in two component enzymes at the same time, the malonyl and palmityl transferases. Among more than 180 fas1 and fas2 mutants systematically screened for malonyl and palmityl transferase activities no mutant was found affected in only one of these two fatty acid synthetase component enzymes. From this it is concluded that both transfer reactions are catalyzed by the same enzyme. In any malonyl transferase‐less fatty acid synthetase, neither of the two known malonyl binding sites, i.e. enzyme‐bound pantetheine and the non‐thiol binding site, accepts malonate. This indicates that malonate is transferred to both groups by the same enzyme. So far, no acetyl transferase‐less fas mutants have been characterized. On the other hand, the mutants of two fas1 complementation groups, Va and Vd, though negative in overall fatty acid synthetase activity had no deficiency in any of the known component enzymes which can be tested in vitro. A possible interrelationship between both findings is discussed.

Amino acid sequence around the active serine in the acyl transferase domain of rabbit mammary fatty acid synthase

“…It is interesting that in yeast the malonyl transferase also catalyses the terminating long chain acyl transferase step [16,17]. This latter activity is totally lacking in the vertebrate enzyme, which uses instead a thioester hydrolase reaction for chain termination.…”

Lipid Biochemistry of Fungi and Other Organisms

“…A new concept of the yeast fatty acid synthetase has emerged and is based on comprehensive genetic and biochemical analyses by Schweizer and his colleagues (Schweizer et al, 1973;Schweizer and Bolling, 1970;Kuhn et al, 1972;Knobling et al, 1975;Schweizer et al, 1971;Tauro et al, 1974;Schweizer et al, 1978). The evidence suggests that the yeast fatty acid synthetase is composed of two multifunctional proteins, designated a and S, with molecular weights of 185,000 and 180,000 daltons, respectively.…”

On the Structure of Fatty Acid Synthetase of Yeast

“…The identity of the two transacylases was proved in different ways: firstly by genetic analysis in Schweizer's laboratory [42], secondly by the binding studies of Engeser [43] in which it was demonstrated that after complete loading of fatty acid synthetase with malonate, no palmitate could be accepted and vice versa. In addition it was found [44] that the radiolabelled peptides isolated by proteolytic digestion of ['"CIpalmitoyl-enzyme of ['4C]malonyl-enzyme possess the same amino acid sequence (Fig.…”