Synthesis of cephalosporin C and sulfur metabolism by methionine analogue resistant mutants of cephalosporium acremonium

Abstract

The biosynthesis of cephalosporin C (CPC) and sulfur metabolism by methionine analogue (DL-selenomethionine) resistant mutants of $\underline{Cephalosprium}$ $\underline{acremonium}$ were studied. In the parent cell, the minimum inhibitory concentration (MIC) of DL-seleno-methionine on growth was $3 \mu g/ml$. There were three main groups in the methionine resistant mutants selected after N``-nitro-N-nitrosoguanidine (NTG) treatment. The first group was the most resistant to DL-seleno-methionine than other mutants and had decreased activity for L-methionine uptake. The second group with increased activity for sulfate uptake and decreased activity for L-methionine uptake, and utilized methionine by somewhat diffusion. The third groups of increased activities for sulfate and L-methionine uptake, accumulated excess methionine from sulfate, and had less inhibitory effects on the function and biosynthesis of sulfate permease by cysteine and methionine than the parent cell. The mutants with increased activity for sulfate uptake produced more CPC from sulfate than the parent cell, and replaced methionine by sulfate as sulfur source in the production of CPC. It was revealed that L-cysteine is an inhibitor and L-methionine is a repressor in the sulfate permease of $\underline{C.}$ $\underline{acremonium}$. And enzymatic studies indicated that L-cysteine might act as a metabolic regulator on the sulfate utilizing enzymes.