Enhanced production of validamycin A by H2O2-induced reactive oxygen species in fermentation of Streptomyces hygroscopicus 5008.
A novel fermentation strategy to enhance antibiotics production was demonstrated by inducing reactive oxygen species (ROS), and validamycin A (VAL-A) production by Streptomyces hygroscopicus 5008 in agro-industrial residues containing medium was taken as an example. By optimizing H2O2 amount and addition time, the intracellular ROS level was increased, and VAL-A production titer was enhanced by 40% on day 4 when 25 μM H2O2 was added at 8th h of fermentation. Addition of diphenyleneiodonium chloride (ROS inhibitor) reduced the H2O2 induction effect. The transcription level of eight VAL-A structure genes was enhanced by ROS, and activities of glucose-6-phosphate dehydrogenase and ValG enzyme were increased while glyceraldehyde 3-phosphate dehydrogenase activity was inhibited. This work demonstrated that ROS induction was a useful strategy for VAL-A fermentation, and the information on gene transcription and enzyme activities may be helpful to further understanding the mechanism of ROS effect on the antibiotic biosynthesis.
Wei
Zhen-Hua
ZH
State Key Laboratory of Bioreactor Engineering, School of Bioengineering, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, China.
Bai
Linquan
L
Deng
Zixin
Z
Zhong
Jian-Jiang
JJ
D005285:Fermentation / Q000187:drug effects*; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D005798:Genes, Bacterial / Q000235:genetics; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism; D016695:Glycosyltransferases / Q000235:genetics / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007294:Inositol / Q000031:analogs & derivatives / Q000096:biosynthesis; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D009861:Onium Compounds / Q000494:pharmacology; D013302:Streptomyces / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics / Q000254:growth & development; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects
D009861:Onium Compounds; C030790:validamycin A; D007294:Inositol; C007517:diphenyleneiodonium; D006861:Hydrogen Peroxide; D005954:Glucosephosphate Dehydrogenase; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D016695:Glycosyltransferases; C531432:ValG protein, Streptomyces hygroscopicus