Continuous‐culture studies on the regulation of tylosin biosynthesis

Abstract

The metabolic regulation of tylosin synthesis by Streptomyces fradiae NRRL 2702 was studied in batch and chemostat cultures using a soluble synthetic medium. In batch culture a medium which diminished the trophophase-idiophase kinetic pattern was used to assess the activities of the enzymes involved in tylosin synthesis. The enzymes methylmalonyl-coenzyme A carboxyltransferase (EC 2.1.3.1) and propionyl-coenzyme A carboxylase (EC 6.4.1.3) showed early enzymatic derepression, both enzymes reaching their highest specific activities after 72-96 fermentation. The activity of macrocin 3' -O-methyltransferase, the enzyme catalyzing the conversion of macrocin (tylosin C) to tylosin (tylosin A). also peaked at 72 h. The specific activities of the three enzymes showed close correlation with the q(tylosin) value. In chemostat cultures the activities of the enzymes and the intracellular level of the adenylate pool and energy charge were studied as a function of dilution rate. Under steady-state conditions, increases in the specific growth rate repressed the enzymes activities with a concomitant increase in the intracellular level of the adenylate pool, while the adenylate energy charge remained almost constant and in the range 0.5-0.52. The highest specific activities of the enzymes were observed when D = 0.008 h (-1). The specific rate of tylosin synthesis was inversely proportional to the specific growth rate and the intracellular level of adenylate pool. The pool of adenylate could be a nutritional parameter which had a considerable influence on the biosynthesis of tylosin.

Assessment of near‐infrared spectral information for rapid monitoring of bioprocess quality

“…A 10% (v/v) inoculum was used to inoculate 10 L of medium A or B in the bioreactor. Medium A (Vu-Trong and Gray, 1982) consisted of (in g/L) methyl oleate-15.0, glucose-5.0, monosodium glutamate-17.5, ammonium ferric citrate-1.5, betaine hydrochloride-2.5, di-potassium hydrogen phosphate-1.15, sodium chloride-1, magnesium sulphate-2.5, calcium chloride 1.5, cobalt chloride-0.0005, and zinc sulphate-0.005. Medium B (Gray and Bhuwapathanapun, 1980) was the same as medium A, except for the levels of glucose and glutamate, which were (in g/L) 17.5 and 10, respectively.…”

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

“…The tylosin factors were analyzed by an HPLC method and other analytical procedures have been previously described (Vu-Trong and Gray, 1982).…”

“…In previous reports Vu-Trong and Gray, 1982), a medium was described which diminished the classical trophophase-idiophase kinetic pattern usually observed in batch tylosin fermentations.…”

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

“…Tylosin fermentations with synthetic media in batch, fedbatch and chemostat cultures have previously been reported (Gray and Bhuwapathanapun, 1980;Bhuwapathanapun and Gray, 198]; Vu-Trong and Gray, 1982a). 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).…”