Effect of fermentation temperature on validamycin A production by Streptomyces hygroscopicus 5008

Validamycin A (VAL-A), produced by Streptomyces hygroscopicus, is an important anti-fungal agro-antibiotic. In this work, the effect of fermentation temperature on VAL-A biosynthesis by S. hygroscopicus 5008 was investigated between 28 °C and 42 °C, and an interesting threshold of temperature for VAL-A biosynthesis was found between 35 °C and 37 °C. At a relatively higher temperature, a much higher VAL-A productivity was obtained together with faster protein synthesis and sugar consumption. Transcriptional analysis of samples from early, middle and late stages of fermentation at various temperatures demonstrated that three operons, valABC, valKLMN and valG, for all eight necessary structure genes, were dramatically promoted when temperature reached the threshold. Activities of both glucose-6-phosphate dehydrogenase (G6PDH) of pentose-phosphate pathway and ValG of VAL-A biosynthesis were also enhanced at a higher cultivation temperature. The interesting temperature effect with a 2 °C threshold shift from 35 °C to 37 °C on the antibiotic biosynthesis was understood to be related to the gene transcriptional levels and key enzyme activities.