Breeding of High-yield Rifamycin SV Strain by Plasma Action Combined with Oxygen Restriction Model

doi:10.13523/j.cb.2010005

China Biotechnology

2021, Vol. 41

Issue (2/3): 38-44 DOI: 10.13523/j.cb.2010005

Breeding of High-yield Rifamycin SV Strain by Plasma Action Combined with Oxygen Restriction Model

LI Bo^1,²,WANG Ze-jian^3,^**(

),LIANG Jian-guang^4,^**(

),LIU Ai-jun⁵,LI Hai-dong⁵

1 School of Biological and Food Engineering,Changshu Institute of Technology,Changshu 215500, China
2 College of Pharmaceutical Science,Soochow University,Suzhou 215123, China
3 State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China
4 College of Pharmaceutical and Life Sciences, Changzhou University,Changzhou 213164, China
5 Hebei Xingang Pharmaceutical Co., Ltd,Hebei 051530,China

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Abstract

Rifamycin SV has low toxicity, high curative effect, and broad antibacterial spectrum. It is mainly produced through the aerobic fermentation by Amycobacterium marinum, and oxygen supply limitation was always the critical factor that affects the rifamycin SV biosynthesis. In order to reduce the influence of oxygen limitation in the fermentation process and further increase the fermentation yield of rifamycin, an oxygen limitation directional model was established with anhydrous sodium sulfite, combining normal temperature and atmospheric pressure plasma mutagenesis(ARTP); a high-throughput screening method of rapid culture of the vinegar-producing strains in 24-well plates was proposed; the high-yielding rifamycin SV strain NSMXG-M126 that can tolerate hypoxia has been efficiently selected. The changes in the parameters of the fermentation metabolic state show that the high-yielding strain has better oxygen affinity. Under the same oxygen supply conditions, it showed a faster bacterial growth rate and rapid synthesis of rifamycin SV compared with the control. In the case of low oxygen supply, the fermentation unit reached 7 839mg/mL, which was 48% higher than the original strain. The results demonstrated that the mutant strains that tolerate hypoxia have higher production efficiency of rifamycin SV.

Key words： Rifamycin SV Amycobacterium marinum High-throughput screening Atmospheric and room temperature plasma (ARTP) Oxygen-limited model

Received: 05 November 2020 Published: 08 April 2021

ZTFLH:

Q815

Corresponding Authors: Ze-jian WANG,Jian-guang LIANG E-mail: wzjvictory@163.com;liang4523@126.com

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Cite this article:

LI Bo,WANG Ze-jian,LIANG Jian-guang,LIU Ai-jun,LI Hai-dong. Breeding of High-yield Rifamycin SV Strain by Plasma Action Combined with Oxygen Restriction Model. China Biotechnology, 2021, 41(2/3): 38-44.

URL:

https://manu60.magtech.com.cn/biotech/10.13523/j.cb.2010005 OR https://manu60.magtech.com.cn/biotech/Y2021/V41/I2/3/38

Table 1 Fermentation conditions of initial strains under different conditions of liquid volume in well plates and comparison with shake flask fermentation

Fig.1 Lethality curve Amycobacterium marinum treated by ARTP

Table 2 Effects of different concentrations of sodium sulfite on colony forming units(CFU)

Table 3 The effect of different treatment time on the positive mutation rate under the condition of oxygen limitation model

Table 4 Verification of strain genetic stability

Table 5 Comparison of fermentation of starting strain and NSMXG-M126 under different oxygen supply conditions in a 50L fermentor

Fig.2 Comparison of fermentation process between starting strain and NSMXG-M126 under low oxygen supply in 50L fermentor


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