The effect of thiolactomycin analogues on fatty acid synthesis in peas (Pisum sativum cv. Onward).

Abstract

Thiolactomycin is an inhibitor of type I1 dissociable fatty acid synthases from plants and bacteria [ 1 1. The three P-ketoacyl acyl carrier protein (ACP) synthases in peas are all inhibited by thiolactomycin [2]. Condensing enzyme I1 (KAS II), which catalyses the elongation of palmitoyl-ACP to stearoyl-ACP is the most sensitive and the short chain condensing enzyme (KAS III), which catalyses the initial condensation of acetyl-CoA with malonyl-ACP, the least sensitive [2]. There is some evidence that acetyl-CoA: ACP transacylase activity is also inhibited but the other enzymes of fatty acid synthesis appear to be unaffected [2, 31. Table 1 shows that several of the analogues produce greater inhibition of fatty acid synthesis than thiolactomycin itself Thiolactomycin has a polar head group and a 5 carbon hydrophobic side chain (see legend to Table 1). Apart from analogue 7, which contains a nitrile group and gave rather inconsistent results, the most effective analogue structures are 5 and 6, both of which are more hydrophobic than thiolactomycin. Analogue 4 which is a straight-chain hydrocarbon but less hydrophobic than thiolactomycin give a inhibition, though not so much as thiolactomycin itself The shorter side chain of analogue 2 and the epoxy side-group of analogue 3 produced no inhibition at all. Hydrophobicity and length of the side chain therefore appear to