Impact of nitrogen concentration on validamycin A production and related gene transcription in fermentation of Streptomyces hygroscopicus 5008

Abstract

Validamycin A (VAL-A) is an important and widely used agricultural antibiotic. In this study, statistical screening designs were applied to identify significant medium variables for VAL-A production and to find their optimal levels. The optimized medium caused 70% enhancement of VAL-A production. The difference between optimized medium and original medium suggested that low nitrogen source level might attribute to the enhancement of VAL-A production. The addition of different nitrogen sources to the optimized medium inhibited VAL-A production, which confirmed the importance of nitrogen concentration for VAL-A production. Furthermore, differences in structural gene transcription and enzyme activity between the two media were assayed. The results showed that lower nitrogen level in the optimized medium could regulate VAL-A production in gene transcriptional level. Our previous study indicated that the transcription of VAL-A structural genes could be enhanced at elevated temperature. In this work, the increased fermentation temperature from 37 to 42 °C with the optimized medium enhanced VAL-A production by 39%, which testified to the importance of structural gene transcription in VAL-A production. The information is useful for further VAL-A production enhancement.

Enhanced production of validamycin A in Streptomyces hygroscopicus 5008 by engineering validamycin biosynthetic gene cluster

“…The highest ValG activity of the two strains was obtained at 72 h, later than its gene transcription, which is in agreement with previous reports (Wei et al 2011(Wei et al , 2012a, and this is in agreement with the central dogma, in which translation starts after gene transcription due to the translational regulation (Vogel and Marcotte 2012). Moreover, it was reported that the bacterial mRNAs are short-lived so that their concentrations are much more fluctuating than the corresponding longer-lived proteins (Vogel and Marcotte 2012).…”

“…These investigations range from process improvement such as medium optimization with agro-industrial residues (Wei et al 2012a), application of fermentation strategies (Wei et al 2012b), and stimulator addition Wei et al 2011;Zhou et al 2012), to metabolic pathways for increasing precursor supply (Zhou et al 2011). For industrial scale production, strain improvement is essential to obtain a relatively high amount of products.…”

Production of validamycin A from hemicellulose hydrolysate by Streptomyces hygroscopicus 5008

“…Recently this antibiotic is also recognized as an important raw material for production of an antidiabetic drug, voglibose (Yu et al, 2005). Because of its commercial significance, enhancing the VAL-A production has been the focus of many investigations during past decades (Wei et al, 2012;Zhou et al, 2014Zhou et al, , 2011. In another aspect, it is evident that reducing the VAL-A production cost is critical to its large-scale production due to its rather low price.…”

Influence of Ammonium Salt and Fermentation pH on Acarbose Yield from <i>Streptomyces</i> M37

“…Many aspects of acarbose fermentation have been well studied and reported, ranging from producer strains, media formula, fermentation conditions, and acarbose isolation and purification [5][6][7][8][9]. The importance of nitrogen sources in industrial microbiology is very significant since it affects the synthesis of enzymes involved in both primary and secondary metabolism [10][11][12]. It is known that glutamate is the primary source of Nglycosidic bond in the biosynthesis of acarbose [13].…”