Significance of oxygen carriers and role of liquid paraffin in improving validamycin A production

Abstract

Validamycin A (Val-A) synthesized by Streptomyces hygroscopicus 5008 is widely used as a high-efficient antibiotic to protect plants from sheath blight disease. A novel fermentation strategy was introduced to stimulate Val-A production by adding oxygen carriers. About 58 % increase in Val-A production was achieved using liquid paraffin. Further, biomass, carbon source, metabolic genes, and metabolic enzymes were studied. It was also found that the supplementation of liquid paraffin increased the medium dissolved oxygen and intracellular oxidative stress level. The expression of the global regulators afsR and soxR sensitive to ROS, ugp catalyzing synthesis of Val-A precursor, and Val-A structural genes was enhanced. The change of the activities of glucose-6-phosphate dehydrogenase and glyceraldehyde 3-phosphate dehydrogenase was observed, which reflected the redirection of carbon metabolic flux. Based on these results, liquid paraffin addition as an oxygen carrier could be a useful technique in industrial production of Val-A and our study revealed a redox-based secondary metabolic regulation in S. hygroscopicus 5008, which provided a new insight into the regulation of the biosynthesis of secondary metabolites.

The Onset of Tacrolimus Biosynthesis in Streptomyces tsukubaensis Is Dependent on the Intracellular Redox Status

“…As the main H 2 O 2 -detoxifying enzyme, the induction of catalase activity can suggest a response to elevated ROS levels and thus a reflection of intracellular oxidative stress [ 31 ]. In order to determine if the induction of catalase activity is due to an increase in intracellular oxidative stress, in particular due to an increase of H 2 O 2 levels, we measured the intracellular ROS levels using a fluorogenic dye (DHR probe) ( Figure 1 d).…”

Biosynthesis and metabolic engineering of pseudo-oligosaccharides

“…In addition to the carbon source, which plays a direct role in pseudo-oligosaccharide biosynthesis, nitrogen concentration (59), temperature (60, 61), alkaline pH shock (62), and intracellular reactive oxygen species (ROS) (63–65) can affect validamycin production in S. hygroscopicus 5008. In contrast to the normal growth and sporulation temperature of actinomycetes, the optimal temperature for validamycin A production is 35-37 °C.…”

“…Under these conditions, the transcription level of most validamycin A biosynthetic genes also increased, except for the glycosyltransferase gene valG . Furthermore, the addition of ethanol (63), hydrogen peroxide (64), or liquid paraffin (65), as well as a temperature shift (61), appears to increase the medium dissolved oxygen and/or the intracellular oxidative stress level. Intracellular ROS was found to act as the molecular signal for the transcription of validamycin A biosynthetic genes.…”