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BioMed Research International Volume 2017 ,2017-01-24
Significance of Heavy-Ion Beam Irradiation-Induced Avermectin B1a Production by Engineered Streptomyces avermitilis
Research Article
Shu-Yang Wang 1 , 2 Yong-Heng Bo 3 Xiang Zhou 1 Ji-Hong Chen 1 Wen-Jian Li 1 Jian-Ping Liang 1 Guo-Qing Xiao 1 Yu-Chen Wang 1 Jing Liu 1 Wei Hu 1 Bo-Ling Jiang 1
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DOI:10.1155/2017/5373262
Received 2016-06-30, accepted for publication 2016-10-23, Published 2016-10-23
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摘要

Heavy-ion irradiation technology has advantages over traditional methods of mutagenesis. Heavy-ion irradiation improves the mutation rate, broadens the mutation spectrum, and shortens the breeding cycle. However, few data are currently available regarding its effect on Streptomyces avermitilis morphology and productivity. In this study, the influence of heavy-ion irradiation on S. avermitilis when cultivated in approximately 10 L stirred-tank bioreactors was investigated. The specific productivity of the avermectin (AVM) B1a-producing mutant S. avermitilis 147-G58 increased notably, from 3885 to 5446 μg/mL, approximately 1.6-fold, compared to the original strain. The mycelial morphology of the mutant fermentation processes was microscopically examined. Additionally, protein and metabolite identification was performed by using SDS-PAGE, 2- and 3-dimensional electrophoresis (2DE and 3DE). The results showed that negative regulation gene deletion of mutants led to metabolic process upregulating expression of protein and improving the productivity of an avermectin B1a. The results showed that the heavy-ion beam irradiation dose that corresponded to optimal production was well over the standard dose, at approximately 80 Gy at 220 AMeV (depending on the strain). This study provides reliable data and a feasible method for increasing AVM productivity in industrial processes.

授权许可

Copyright © 2017 Shu-Yang Wang et al. 2017
This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

图表

Growth kinetics of the original strain and the mutant strains AO-M31, HS-P18, and 147-G58 cultivated with shaking. (a) Time course of the cell dry weight and dextrin consumption of the original strain and the mutant strains AO-M31, HS-P18, and 147-G58. Left panel, comparison of the AO-M31 mutant (black circles and black triangles) with original strain S. avermitilis (white circles and white triangles). Middle panel, comparison of the 147-G58 mutant (black circles and black triangles) with original strain S. avermitilis (white circles and white triangles). Right panel, comparison of the HS-P18 mutant (black circles and black triangles) with original strain S. avermitilis (white circles and white triangles). (b) Time profiles of the AVM B1a specific productivity of original strain and AO-M31, HS-P18, and 147-G58 mutant. On the left is comparison of AO-M31 mutant (black box) with the original strain S. avermitilis (white box), the comparison of 147-G58 mutant (black box) with the original strains S. avermitilis (white box) is in the middle, and on the right is comparison of HS-P18 mutant (black box) with the original strains avermitilis (white box). Data are the average of quintuplicate samples; the error bars indicate the standard deviations. All results were analyzed with Tukey’s test (duplicate determinations, p ∗ ∗ < 0.01 ).

Growth kinetics of the original strain and the mutant strains AO-M31, HS-P18, and 147-G58 cultivated with shaking. (a) Time course of the cell dry weight and dextrin consumption of the original strain and the mutant strains AO-M31, HS-P18, and 147-G58. Left panel, comparison of the AO-M31 mutant (black circles and black triangles) with original strain S. avermitilis (white circles and white triangles). Middle panel, comparison of the 147-G58 mutant (black circles and black triangles) with original strain S. avermitilis (white circles and white triangles). Right panel, comparison of the HS-P18 mutant (black circles and black triangles) with original strain S. avermitilis (white circles and white triangles). (b) Time profiles of the AVM B1a specific productivity of original strain and AO-M31, HS-P18, and 147-G58 mutant. On the left is comparison of AO-M31 mutant (black box) with the original strain S. avermitilis (white box), the comparison of 147-G58 mutant (black box) with the original strains S. avermitilis (white box) is in the middle, and on the right is comparison of HS-P18 mutant (black box) with the original strains avermitilis (white box). Data are the average of quintuplicate samples; the error bars indicate the standard deviations. All results were analyzed with Tukey’s test (duplicate determinations, p ∗ ∗ < 0.01 ).

Comparison of the mycelial morphology between original strain avermitilis and the 147-G58 mutant with optimized agitation at 250 rpm at different time points.

2DE and 3DE gels of soluble proteins to determine the most highly expressed proteins of the S. avermitilis original strain, HS-P18, and 147-G58 mutants. (a) The soluble proteins with the highest expression levels in original strain, HS-P18, and 147-G58 mutants were identified on 2DE gels. (b) The 3 strains were analyzed by 3DE in the ranges of 29 kDa and 4.2 pI. (c) The 3 strains were analyzed by 3DE in the ranges of 40.5 kDa and 5.1 pI. The figure shows that the expression of the 147-G58 mutant was higher than that of original strain, although expression was only weakly observed.

2DE and 3DE gels of soluble proteins to determine the most highly expressed proteins of the S. avermitilis original strain, HS-P18, and 147-G58 mutants. (a) The soluble proteins with the highest expression levels in original strain, HS-P18, and 147-G58 mutants were identified on 2DE gels. (b) The 3 strains were analyzed by 3DE in the ranges of 29 kDa and 4.2 pI. (c) The 3 strains were analyzed by 3DE in the ranges of 40.5 kDa and 5.1 pI. The figure shows that the expression of the 147-G58 mutant was higher than that of original strain, although expression was only weakly observed.

2DE and 3DE gels of soluble proteins to determine the most highly expressed proteins of the S. avermitilis original strain, HS-P18, and 147-G58 mutants. (a) The soluble proteins with the highest expression levels in original strain, HS-P18, and 147-G58 mutants were identified on 2DE gels. (b) The 3 strains were analyzed by 3DE in the ranges of 29 kDa and 4.2 pI. (c) The 3 strains were analyzed by 3DE in the ranges of 40.5 kDa and 5.1 pI. The figure shows that the expression of the 147-G58 mutant was higher than that of original strain, although expression was only weakly observed.

Time course of the physiological working capacity of 147-G58 mutants cultivated in stirred-tank bioreactors with different agitation speeds. (a) Time course of cell dry weight with agitation speeds of 150, 250, and 350 rpm. (b) Time course of dextrin consumption with agitation speeds 150, 250, and 350 rpm. (c) Time course of the AVM B1a specific productivity with agitation speeds 150, 250, and 350 rpm. (d) Time course of the dash dotted line of DO-levels with agitation speeds 150, 250, and 350 rpm. (e) Time course of determination of oxygen uptake rate (OUR) with agitation speeds 150, 250, and 350 rpm. (f) Time course of determination of the specific oxygen uptake rate (SOUR) with agitation speeds 150, 250, and 350 rpm. Black circle symbol for 150 rpm speeds, grey circle symbol for 250 rpm speeds, and off-white circle symbol for 350 rpm speeds, respectively.

Time course of the physiological working capacity of 147-G58 mutants cultivated in stirred-tank bioreactors with different agitation speeds. (a) Time course of cell dry weight with agitation speeds of 150, 250, and 350 rpm. (b) Time course of dextrin consumption with agitation speeds 150, 250, and 350 rpm. (c) Time course of the AVM B1a specific productivity with agitation speeds 150, 250, and 350 rpm. (d) Time course of the dash dotted line of DO-levels with agitation speeds 150, 250, and 350 rpm. (e) Time course of determination of oxygen uptake rate (OUR) with agitation speeds 150, 250, and 350 rpm. (f) Time course of determination of the specific oxygen uptake rate (SOUR) with agitation speeds 150, 250, and 350 rpm. Black circle symbol for 150 rpm speeds, grey circle symbol for 250 rpm speeds, and off-white circle symbol for 350 rpm speeds, respectively.

Time course of the physiological working capacity of 147-G58 mutants cultivated in stirred-tank bioreactors with different agitation speeds. (a) Time course of cell dry weight with agitation speeds of 150, 250, and 350 rpm. (b) Time course of dextrin consumption with agitation speeds 150, 250, and 350 rpm. (c) Time course of the AVM B1a specific productivity with agitation speeds 150, 250, and 350 rpm. (d) Time course of the dash dotted line of DO-levels with agitation speeds 150, 250, and 350 rpm. (e) Time course of determination of oxygen uptake rate (OUR) with agitation speeds 150, 250, and 350 rpm. (f) Time course of determination of the specific oxygen uptake rate (SOUR) with agitation speeds 150, 250, and 350 rpm. Black circle symbol for 150 rpm speeds, grey circle symbol for 250 rpm speeds, and off-white circle symbol for 350 rpm speeds, respectively.

Time course of the physiological working capacity of 147-G58 mutants cultivated in stirred-tank bioreactors with different agitation speeds. (a) Time course of cell dry weight with agitation speeds of 150, 250, and 350 rpm. (b) Time course of dextrin consumption with agitation speeds 150, 250, and 350 rpm. (c) Time course of the AVM B1a specific productivity with agitation speeds 150, 250, and 350 rpm. (d) Time course of the dash dotted line of DO-levels with agitation speeds 150, 250, and 350 rpm. (e) Time course of determination of oxygen uptake rate (OUR) with agitation speeds 150, 250, and 350 rpm. (f) Time course of determination of the specific oxygen uptake rate (SOUR) with agitation speeds 150, 250, and 350 rpm. Black circle symbol for 150 rpm speeds, grey circle symbol for 250 rpm speeds, and off-white circle symbol for 350 rpm speeds, respectively.

Time course of the physiological working capacity of 147-G58 mutants cultivated in stirred-tank bioreactors with different agitation speeds. (a) Time course of cell dry weight with agitation speeds of 150, 250, and 350 rpm. (b) Time course of dextrin consumption with agitation speeds 150, 250, and 350 rpm. (c) Time course of the AVM B1a specific productivity with agitation speeds 150, 250, and 350 rpm. (d) Time course of the dash dotted line of DO-levels with agitation speeds 150, 250, and 350 rpm. (e) Time course of determination of oxygen uptake rate (OUR) with agitation speeds 150, 250, and 350 rpm. (f) Time course of determination of the specific oxygen uptake rate (SOUR) with agitation speeds 150, 250, and 350 rpm. Black circle symbol for 150 rpm speeds, grey circle symbol for 250 rpm speeds, and off-white circle symbol for 350 rpm speeds, respectively.

Time course of the physiological working capacity of 147-G58 mutants cultivated in stirred-tank bioreactors with different agitation speeds. (a) Time course of cell dry weight with agitation speeds of 150, 250, and 350 rpm. (b) Time course of dextrin consumption with agitation speeds 150, 250, and 350 rpm. (c) Time course of the AVM B1a specific productivity with agitation speeds 150, 250, and 350 rpm. (d) Time course of the dash dotted line of DO-levels with agitation speeds 150, 250, and 350 rpm. (e) Time course of determination of oxygen uptake rate (OUR) with agitation speeds 150, 250, and 350 rpm. (f) Time course of determination of the specific oxygen uptake rate (SOUR) with agitation speeds 150, 250, and 350 rpm. Black circle symbol for 150 rpm speeds, grey circle symbol for 250 rpm speeds, and off-white circle symbol for 350 rpm speeds, respectively.

通讯作者

Shu-Yang Wang.Institute of Modern Physics, Chinese Academy of Sciences, 509 Nanchang Rd., Lanzhou, Gansu 730000, China, cas.cn;Lanzhou University, 222 South Tianshui Road, Lanzhou, Gansu 730000, China, lzu.edu.cn.wangsy@impcas.ac.cn

推荐引用方式

Shu-Yang Wang,Yong-Heng Bo,Xiang Zhou,Ji-Hong Chen,Wen-Jian Li,Jian-Ping Liang,Guo-Qing Xiao,Yu-Chen Wang,Jing Liu,Wei Hu,Bo-Ling Jiang. Significance of Heavy-Ion Beam Irradiation-Induced Avermectin B1a Production by Engineered Streptomyces avermitilis. BioMed Research International ,Vol.2017(2017)

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