Uncovering the Effects of Ammonium Sulfate on Neomycin B Biosynthesis in <i>Streptomyces fradiae</i> SF-2
Xiangfei Li,
Fei Yu,
Kun Liu,
Min Zhang,
Yihan Cheng,
Fang Wang,
Shan Wang,
Rumeng Han,
Zhenglian Xue
Affiliations
Xiangfei Li
Engineering Laboratory for Industrial Microbiology Molecular Beeding of Anhui Province, College of Biologic & Food Engineering, Anhui Polytechnic University, Wuhu 241000, China
Fei Yu
Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, China
Kun Liu
Engineering Laboratory for Industrial Microbiology Molecular Beeding of Anhui Province, College of Biologic & Food Engineering, Anhui Polytechnic University, Wuhu 241000, China
Min Zhang
Engineering Laboratory for Industrial Microbiology Molecular Beeding of Anhui Province, College of Biologic & Food Engineering, Anhui Polytechnic University, Wuhu 241000, China
Yihan Cheng
Engineering Laboratory for Industrial Microbiology Molecular Beeding of Anhui Province, College of Biologic & Food Engineering, Anhui Polytechnic University, Wuhu 241000, China
Fang Wang
Engineering Laboratory for Industrial Microbiology Molecular Beeding of Anhui Province, College of Biologic & Food Engineering, Anhui Polytechnic University, Wuhu 241000, China
Shan Wang
Engineering Laboratory for Industrial Microbiology Molecular Beeding of Anhui Province, College of Biologic & Food Engineering, Anhui Polytechnic University, Wuhu 241000, China
Rumeng Han
Engineering Laboratory for Industrial Microbiology Molecular Beeding of Anhui Province, College of Biologic & Food Engineering, Anhui Polytechnic University, Wuhu 241000, China
Zhenglian Xue
Engineering Laboratory for Industrial Microbiology Molecular Beeding of Anhui Province, College of Biologic & Food Engineering, Anhui Polytechnic University, Wuhu 241000, China
The aminoglycoside antibiotic neomycin has broad antibacterial properties and is widely used in medicine and agriculture. With the discovery of neomycin’s potential applications in treating tumors and SARS-CoV-2, it is necessary to accelerate the biosynthesis of neomycin. In the present study, we investigated the effects of various inorganic salts on neomycin B (the main active neomycin) biosynthesis in Streptomyces fradiae SF-2. We found that 60 mM (NH4)2SO4 could promote neomycin B biosynthesis and cell growth most effectively. Further comparative transcriptomic analyses revealed that 60 mM (NH4)2SO4 inhibited the EMP and TCA cycles and enhanced the expression of neo genes involved in the neomycin B biosynthesis pathway. Finally, a neomycin B potency of 17,399 U/mL in shaking flasks was achieved by overexpressing neoE and adding 60 mM (NH4)2SO4, corresponding to a 51.2% increase compared with the control S. fradiae SF-2. In the present study, the mechanism by which (NH4)2SO4 affects neomycin biosynthesis was revealed through transcriptomics, providing a reference for the further metabolic engineering of S. fradiae SF-2 for neomycin B production.
