Dynamics of L-valine in relation to the production of cyclosporin A by Tolypocladium inflatum.
We report the kinetics of endogenous L-valine in the fungus Tolypocladium inflatum, in an effort to understand the enhancing effect of externally supplemented L-valine on the production of the immunosuppressant cyclosporin A (CyA) in chemically defined medium. In a batch laboratory stirred reactor cultivation, the concentration of intracellular L-valine increased by up to four times between the end of the exponential phase and the beginning of the stationary phase when the medium was supplemented externally with 4 g/l L-valine. The final CyA titre under these conditions was 710 mg/l compared to only 130 mg/l attained without L-valine supplementation. In contrast to substantial growth-associated production of CyA in unsupplemented culture, the formation of the immunosuppressant was prolonged during the stationary phase in L-valine-supplemented medium. As a result, the conversion yield of CyA on L-valine remained constant during the stationary phase at 0.27 g CyA/g L-valine.
Department of Chemical and Biochemical Engineering, State University of New Jersey, Piscataway 08855-0909.
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Lee
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Agathos
D003524:Cyclosporins / Q000378:metabolism*; D005285:Fermentation; D005658:Fungi / Q000254:growth & development / Q000378:metabolism*; D007700:Kinetics; D014633:Valine / Q000378:metabolism*
D003524:Cyclosporins; D014633:Valine