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.
State Key Laboratory of Bioreactor Engineering, School of Bioengineering, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, China.
Zhen-Hua
ZH
Wei
Linquan
L
Bai
Zixin
Z
Deng
Jian-Jiang
JJ
Zhong
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