Mutation breeding of high avermectin B1a-producing strain by the combination of high energy carbon heavy ion irradiation and sodium nitrite mutagenesis based on high throughput screening

Song, Xiaoqing; Zhang, Yun; Zhu, Xu-Dong; Wang, Yonghong; Chu, Ju; Zhuang, Yingping

doi:10.1007/s12257-017-0022-6

Cited by 17 publications

(7 citation statements)

References 35 publications

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“…We report a method for screening high-yielding strains of doramectin. Mutagenesis is a cost-effective method for the creation of high-yielding strains, Song et al studied a genetic mutant Streptomyces avermitilis S-233 with high-avermectins B1a by comobtained treatment with carbon heavy ion irradiation and sodium nitrite, and Xu et al obtained a strain Streptomyces viridochromogenes F-23 with high-avilamycin production by combined mutagenesis with UV and ARTP [23,33]. The growth of the strains was inhibited by CHC, which is consistent with literature reports [21].…”

Section: Discussionsupporting

confidence: 71%

“…Currently, mutant selection and precursor addition strategies are effective methods to improve the yield of avermectin [22][23][24][25]. In industrial production, CHC is the starting precursor substance for the biosynthesis of doramectin by S. avermitilis, but CHC has an inhibitory effect on the growth of the bacterium, thus affecting the yield of doramectin [21,26].…”

Section: Introductionmentioning

confidence: 99%

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Improved Fermentation Yield of Doramectin from Streptomyces avermitilis N72 by Strain Selection and Glucose Supplementation Strategies

Pan

Cai

2023

Fermentation

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Doramectin is a macrolide antiparasitic that is widely used in the treatment of mammalian parasitic diseases. Doramectin is usually produced by Streptomyces avermitilis fermentation using cyclohexanecarboxylic acid (CHC) as a precursor; however, the growth of S. avermitilis is usually inhibited by CHC, resulting in a low fermentation yield of doramectin. In this study, a high-yielding strain XY-62 was obtained using the S. avermitilis mutant strain S. avermitilis N72 as the starting strain, then combined with a CHC tolerance screening strategy using ultraviolet and nitrosoguanidine mutagenesis, and a 96 microtiter plate solid-state fermentation primary sieving and shake flask fermentation rescreening method. Compared with S. avermitilis N72, the doramectin fermentation yield increased by more than 1.3 times, and it was more adaptable to temperature, pH, and CHC concentration of the culture; additionally, the viability of the mycelial growth was enhanced. In addition, further studies on the high-yielding strain XY-62 revealed that the accumulation of doramectin could be further increased by glucose supplementation during the fermentation process, and the yield of doramectin reached 1068 μg/mL by scaling up the culture in 50 L fermenters; this has the potential for industrial production. Therefore, mutagenesis combined with CHC tolerance screening is an effective way to enhance the fermentation production of doramectin by S. avermitilis. Our strategy and findings can help to improve the production of doramectin in industrial strains of S. avermitilis.

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Section: Discussionsupporting

confidence: 71%

Section: Introductionmentioning

confidence: 99%

Improved Fermentation Yield of Doramectin from Streptomyces avermitilis N72 by Strain Selection and Glucose Supplementation Strategies

Pan

Cai

2023

Fermentation

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“…Compared with traditional mutagenesis technology, as an advanced and e cient mutagenesis technology, heavy ion beam irradiation results in high mutagenesis rates and yields relatively stable mutants, leading to its broad applications as a tool for creating new species. In terms of microbial breeding, approximately 30 genera have been subjected to heavy ion beam irradiation to produce novel strains [29][30][31]. Cadmium resistance of Arthrobacter mutants selected by carbon ion beam irradiation was increased by 2-fold [32], and Lu et al [33] increased the fermentation rate of Saccharomyces cerevisiae subjected to carbon ion beam irradiation by 25%.…”

Section: Introductionmentioning

confidence: 99%

Clostridium acetobutylicum bacterial membrane responses to carbon ion beam irradiation perturbations

Gao¹,

Xiang²,

Zhang³

et al. 2020

Preprint

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Background Clostridium acetobutylicum is an important strain during acetone-butanol-ethanol (ABE) fermentation. However, butanol has toxic effects on cells, limiting the application of ABE fermentation. Accordingly, in this study, we aimed to elucidate the metabolic mechanisms through which Clostridium adapts to butanol stress to facilitate the industrial utilization of Clostridium. Results First, using cell morphology, cell membrane permeability and membrane potential, cell surface hydrophobicity, and cell membrane fatty acid composition analyses in wild-type (ATCC 824) and butanol-tolerant (Y217) strains under butanol stress, we explored the responses in the cell membrane to evaluate the damage caused by butanol poisoning. After 2.0% (v/v) butanol treatment, the extracellular conductivity of ATCC 824 increased, intracellular proteins and nucleotides were released in large quantities, the fluorescein diacetate staining rate decreased, the membrane potential decreased, and the cell membrane permeability increased. Under butanol shock, the cell surface of Y217 cells remained intact, and its butanol tolerance mechanism increased the integrity of cell membrane and reduced leakage of cell contents caused by changed in cell membrane permeability, thereby preventing butanol damage to the cell membrane. When stimulated with butanol, Y217 cells showed reduced surface hydrophobicity, thereby improving cellular tolerance to butanol. A comparison of differences in fatty acid compositions between ATCC 824 and Y217 cell membranes under butanol stress further demonstrated that maintenance of the normal physiological characteristics of cell membranes played important roles in resisting the impact of organic solvents. Conclusions Our findings clarified the changes in physiological and biochemical characteristics of the mutant Y217 cell membrane stimulated with butanol to enhance its tolerance. These results may provide important theoretical guidance for further accelerating the acquisition of bacteria with high butanol tolerance and promoting butanol production. Moreover, our study provided a scientific basis for improving the industrial and environmental adaptability of Clostridium.

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“…Mutations are induced by misrepaired damage. Thus, a high mutation rate and wide mutation spectrum are easier to obtain from mutation breeding using HI (Song et al 2017).…”

Section: Introductionmentioning

confidence: 99%

“Saddle-shaped” dose-survival effect, is it a general and valuable phenomenon in microbes in response to heavy ion beam irradiation?

et al. 2019

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We aimed to verify the Bsaddle-shaped^dose-survival effect of microbes in response to heavy ion beam irradiation (HI), and further determine the radiation parameter that affects saddle shape formation, and the relationship between the saddle region and the positive mutation rate. A bibliometric analysis was performed based on literature containing the dose-survival effect of microbes in response to HI, from which the data on the particle energies, ionic types, irradiated microbes, survival curves, and maximum positive mutation rates were assembled. Articles reporting a Bsaddle-shaped^survival curve accounted for 64% of the total relevant articles and possessed a high cited frequency. The predominant articles, authors, and institutions that reported the dose-survival effect of microbes in response to HI proposed the Bsaddle-shaped^survival curve. It was customarily low-energy (but not moderate-or high-energy) HI that induced the Bsaddle-shaped^dose-survival effect. In addition, the Bsaddle-shapedd ose-survival effect was general among~30-genera microbes. More importantly, most of the saddle regions contained the survival fractions within 10-30%, which are customarily used to screen mutants due to a high positive mutation rate. Further, 87% of the maximum positive mutation rates were associated with the saddle region, and 58% were located in the peak of the saddle region. BSaddle-shaped^dose-survival effect is a reliable and general phenomenon among varieties of microbes customarily in response to low-energy HI. Meanwhile, saddle region is always accompanied with high positive mutation rates. Thus, this study will aid in microbial mutation breeding practices.

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Mutation breeding of high avermectin B1a-producing strain by the combination of high energy carbon heavy ion irradiation and sodium nitrite mutagenesis based on high throughput screening

Cited by 17 publications

References 35 publications

Improved Fermentation Yield of Doramectin from Streptomyces avermitilis N72 by Strain Selection and Glucose Supplementation Strategies

Improved Fermentation Yield of Doramectin from Streptomyces avermitilis N72 by Strain Selection and Glucose Supplementation Strategies

Clostridium acetobutylicum bacterial membrane responses to carbon ion beam irradiation perturbations

“Saddle-shaped” dose-survival effect, is it a general and valuable phenomenon in microbes in response to heavy ion beam irradiation?

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