Stimulation of tylosin productivity resulting from cyclic feeding profiles in fed batch cultures

Abstract

AUSTRALIA SL~IARY Batch fermentations for the production of the macrolide antiobiotic tylosin were carried out with a medium in which the maximum specific rate of tylosin synthesis (qtylosin) occurred while the producer organism Streptomyces fradiae, was actively growlng.With this medium, the value of qtylosin decreased rapidly throughout the fermentation.By using a microprocessor to control the feeding of monosodium glutamate, and glucose in cyclic square wave profiles, it was possible to minimize the decrease in qtvlosin observed in the control and to maintain a linear volumetric accretion ~ate of tylosin resulting in a 114% increase over control in the 250 hour tylosin titre.

Stimulation of enzymes involved in tylosin biosynthesis by cyclic feeding profiles in fed batch cultures

“…It may be that the cyclic feeding pattern allows bursts of protein synthesis which maintain enzymes involved in tylosin biosynthesis at high levels, followed by periods of derepressed conditions, and for this reason higher qtylosins are observed in cyclic fed-batch fermentations than in fermentation where the nutrients are fed at constant rates (Vu-Trong and Gray, 1982b and1982c). sol~d lines: cyclic ~ed batch; 100% activity of pc is 0.04x10-, of mt 4.85xi0-, and of mm 0.96xi0-Units/mg protein)…”

“…When tylosin was produced on a synthetic medium (medium M3) which contains a high glutamate/glucose ratio, the classical trophaseidiophase kinetic pattern usually observed in tylosin batch cultures was diminished (Gray and Bhuwapathanapun, 1980). In previous reports (Vu-Trong and Gray, 1982b and1982c), a fed-batch fermentation process was described which minimised the qtylosin decay observed in the conventional batch and greatly increased the antibiotic productivity.…”