Application of Omics Techniques in Incluced Breecling via Heavy Ion Beam Irradiating Microorganisms

doi:10.13560/j.cnki.biotech.bull.1985.2022-0958

Abstract

Abstract:

Heavy ion beam（HIB）irradiation, with high mutagenesis rate, broad mutagenesis spectrum and stable mutant, has been widely used in the implementation of industrial microbial breeding. With the development of sequencing technology, a more comprehensive understanding of the biological information at multiple levels such as genome, transcriptome, proteome, and metabolome may be achieved via study on the mutagenesis effect of HIB. This paper summarizes the research progress of microbial breeding using HIB, combining high-throughput sequencing technology to explore the biological effects of heavy ion mutagenesis. On this basis, a new idea of using omics methods to study the mutagenesis effect of HIB was further discussed with aim to provide references and suggestions for the breeding technology.

Key words: heavy ion beam irradiation, microbial mutagenesis breeding, multi-omics

LEI Cai-rong, GUO Xiao-peng, CHAI Ran, ZHANG Miao-miao, REN Jun-le, LU Dong. Application of Omics Techniques in Incluced Breecling via Heavy Ion Beam Irradiating Microorganisms[J]. Biotechnology Bulletin, 2023, 39(5): 54-62.

Figures/Tables 2

References 74

[1]	Tanaka A, Shikazono N, Hase Y. Studies on biological effects of ion beams on lethality, molecular nature of mutation, mutation rate, and spectrum of mutation phenotype for mutation breeding in higher plants[J]. J Radiat Res, 2010, 51(3): 223-233. pmid: 20505261
[2]	Matuo Y, Izumi Y, Furusawa Y, et al. Biological effects of carbon ion beams with various LETs on budding yeast Saccharomyces cerevisiae[J]. Mutat Res, 2018, 810: 45-51. doi: 10.1016/j.mrfmmm.2017.10.003 URL
[3]	Luo SW, Zhou LB, Li WJ, et al. Mutagenic effects of carbon ion beam irradiations on dry Lotus japonicus seeds[J]. Nucl Instrum Methods Phys Res Sect B Beam Interact Mater Atoms, 2016, 383: 123-128. doi: 10.1016/j.nimb.2016.06.021 URL
[4]	Feng HY, Yu ZL, Chu PK. Ion implantation of organisms[J]. Mater Sci Eng R Rep, 2006, 54(3/4): 49-120. doi: 10.1016/j.mser.2006.11.001 URL
[5]	Liu L, Hu W, Li WJ, et al. Heavy-ion mutagenesis significantly enhances enduracidin production by Streptomyces fungicidicus[J]. Eng Life Sci, 2018, 19(2): 112-120. doi: 10.1002/elsc.201800109 URL
[6]	Song XQ, Zhang Y, Zhu XD, et al. Mutation breeding of high avermectin B_1a-producing strain by the combination of high energy carbon heavy ion irradiation and sodium nitrite mutagenesis based on high throughput screening[J]. Biotechnol Bioprocess Eng, 2017, 22(5): 539-548. doi: 10.1007/s12257-017-0022-6
[7]	Zhang HD, Lu D, Li X, et al. Heavy ion mutagenesis combined with triclosan screening provides a new strategy for improving the arachidonic acid yield in Mortierella alpina[J]. BMC Biotechnol, 2018, 18(1): 23. doi: 10.1186/s12896-018-0437-y
[8]	麻和平, 彭章普, 张文齐, 等. 重离子束辐照选育高产细菌素植物乳杆菌[J]. 食品工业科技, 2021, 42(15): 139-143.
	Ma HP, Peng ZP, Zhang WQ, et al. Study on mutation breeding of high-yield bacteriocin Lactobacillus plantarum by heavy ion beam irradiation[J]. Sci Technol Food Ind, 2021, 42(15): 139-143.
[9]	Takeshita T, Ivanov I, Oshima K, et al. Comparison of lipid productivity of Parachlorella kessleri heavy-ion beam irradiation mutant PK4 in laboratory and 150-L mass bioreactor, identification and characterization of its genetic variation[J]. Algal Research, 2018, 35: 416-426. doi: 10.1016/j.algal.2018.09.005 URL
[10]	Liang Y, Li SW, Song XD, et al. Swainsonine producing performance of Alternaria oxytropis was improved by heavy-ion mutagenesis technology[J]. FEMS Microbiol Lett, 2021, 368(8): fnab047. doi: 10.1093/femsle/fnab047 URL
[11]	郭晓鹏. 基于酿酒酵母模型的重离子束辐射诱变机理及线粒体相关功能研究[D]. 北京: 中国科学院大学(中国科学院近代物理研究所), 2020.
	Guo XP. Study on mechanism of mutagenesis induced by heavy ion beam irradiation and mitochondrion-related function based on Saccharomyces cerevisiae model[D]. Beijing: Institute of Physics, Chinese Academy of Sciences, 2020.
[12]	Zhang X, Zhang XF, Li HP, et al. Atmospheric and room temperature plasma(ARTP)as a new powerful mutagenesis tool[J]. Appl Microbiol Biotechnol, 2014, 98(12): 5387-5396. doi: 10.1007/s00253-014-5755-y pmid: 24769904
[13]	Chen Y, Tian XW, Li QH, et al. Target-site directed rational high-throughput screening system for high sophorolipids production by Candida bombicola[J]. Bioresour Technol, 2020, 315: 123856. doi: 10.1016/j.biortech.2020.123856 URL
[14]	刘建光, 王永强, 赵贵元, 等. 重离子辐照诱变育种应用及其生物学效应研究进展[J]. 作物杂志, 2016(3): 12-16.
	Liu JG, Wang YQ, Zhao GY, et al. Advances of heavy ion beam application in plant breeding and their biological effect[J]. Crops, 2016(3): 12-16.
[15]	余增亮, 何建军, 邓建国, 等. 离子注入水稻诱变育种机理初探[J]. 安徽农业科学, 1989, 17(1): 12-16.
	Yu ZL, He JJ, Deng JG, et al. Preliminary studies on the mutaqenic mechanism of the ion implamtati on rice[J]. J Anhui Agric Sci, 1989, 17(1): 12-16.
[16]	Li Q. Biomedical research with heavy ions at the IMP accelerators[J]. Adv Space Res, 2007, 40(4): 455-460. doi: 10.1016/j.asr.2007.03.096 URL
[17]	Cao L, Gao Y, Wang XZ, et al. A series of efficient umbrella modeling strategies to track irradiation mutation strains improving butyric acid production from the pre-development earlier stage point of view[J]. Frontiers in Bioengineering and Biotechnology, 2021, 9: 609345. doi: 10.3389/fbioe.2021.609345 URL
[18]	缪建顺, 曹国珍, 张苗苗, 等. 重离子束诱变选育谷氨酸高产菌株[J]. 辐射研究与辐射工艺学报, 2015(5): 37-43.
	Miao JS, Cao GZ, Zhang MM, et al. High-yield glutamic acid strain screened by heavy ion irradiation[J]. J Radiat Res Radiat Process, 2015(5): 37-43.
[19]	高越, 杨阳, 张苗苗, 等. 碳离子束辐照诱变选育丁醇耐受菌株[J]. 辐射研究与辐射工艺学报, 2019, 37(1): 44-49.
	Gao Y, Yang Y, Zhang MM, et al. Carbon ion-beam irradiation screening of a butanol-tolerant mutant of Clostridium acetobutylicum[J]. J Radiat Res Radiat Process, 2019, 37(1): 44-49.
[20]	Li X, Wang J, Tan ZL, et al. Cd resistant characterization of mutant strain irradiated by carbon-ion beam[J]. J Hazard Mater, 2018, 353: 1-8. doi: S0304-3894(18)30188-2 pmid: 29627672
[21]	Dong MY, Wang SY, Xiao GQ, et al. Cellulase production by Aspergillus fumigatus MS13.1 mutant generated by heavy ion mutagenesis and its efficient saccharification of pretreated sweet sorghum straw[J]. Process Biochem, 2019, 84: 22-29. doi: 10.1016/j.procbio.2019.06.006 URL
[22]	Xi YM, Yin L, Chi ZY, et al. Characterization and RNA-seq transcriptomic analysis of a Scenedesmus obliqnus mutant with enhanced photosynthesis efficiency and lipid productivity[J]. Sci Rep, 2021, 11(1): 11795. doi: 10.1038/s41598-021-88954-6
[23]	Xi YM, Liu Y, Chi ZY, et al. Photosynthetic profiling of a Dunaliella salina mutant DS240G-1 with improved β-carotene productivity induced by heavy ions irradiation[J]. Int J Agric Biol Eng, 2021, 14(2): 211-217.
[24]	Wang SY, Bo YH, Zhou X, et al. Significance of heavy-ion beam irradiation-induced avermectin b_1a production by engineered Streptomyces avermitilis[J]. Biomed Res Int, 2017, 2017: 5373262.
[25]	Lesniak W, Pietkiewicz J, Podgorski W. Citric acid fermentation from starch and dextrose syrups by a tracemetal resistant mutant of Aspergillus niger[J]. Biotechnology Letters, 2002, 24(13): 1065-1067. doi: 10.1023/A:1016030513270 URL
[26]	Hu W, Liu J, Chen JH, et al. A mutation of Aspergillus niger for hyper-production of citric acid from corn meal hydrolysate in a bioreactor[J]. J Zhejiang Univ Sci B, 2014, 15(11): 1006-1010. doi: 10.1631/jzus.B1400132 URL
[27]	Wang BS, Chen J, Li H, et al. Pellet-dispersion strategy to simplify the seed cultivation of Aspergillus niger and optimize citric acid production[J]. Bioprocess Biosyst Eng, 2017, 40(1): 45-53. doi: 10.1007/s00449-016-1673-y URL
[28]	Fu J, Chen T, Lu H, et al. Enhancement of docosahexaenoic acid production by low-energy ion implantation coupled with screening method based on Sudan black B staining in Schizochytrium sp.[J]. Bioresour Technol, 2016, 221: 405-411. doi: 10.1016/j.biortech.2016.09.058 URL
[29]	Li SW, Li M, Song HP, et al. Induction of a high-yield lovastatin mutant of Aspergillus terreus by ¹²C⁶⁺ heavy-ion beam irradiation and the influence of culture conditions on lovastatin production under submerged fermentation[J]. Appl Biochem Biotechnol, 2011, 165(3/4): 913-925. doi: 10.1007/s12010-011-9308-x URL
[30]	Li ZZ, Chen XJ, Li ZL, et al. Strain improvement of Trichoderma viride for increased cellulase production by irradiation of electron and¹²C⁶⁺-ion beams[J]. Biotechnol Lett, 2016, 38(6): 983-989. doi: 10.1007/s10529-016-2066-7 URL
[31]	Yamada K, Suzuki H, Takeuchi T, et al. Efficient selective breeding of live oil-rich Euglena gracilis with fluorescence-activated cell sorting[J]. Sci Rep, 2016, 6: 26327. doi: 10.1038/srep26327 pmid: 27212384
[32]	Gao Y, Zhang MM, Zhou X, et al. Effects of carbon ion beam irradiation on butanol tolerance and production of Clostridium acetobutylicum[J]. Front Microbiol, 2020, 11: 602774. doi: 10.3389/fmicb.2020.602774 URL
[33]	Cao GZ, Zhang MM, Miao JS, et al. Effects of X-ray and carbon ion beam irradiation on membrane permeability and integrity in Saccharomyces cerevisiae cells[J]. J Radiat Res, 2015, 56(2): 294-304. doi: 10.1093/jrr/rru114 URL
[34]	Zhang MM, Cao GZ, Guo XP, et al. A comet assay for DNA damage and repair after exposure to carbon-ion beams or X-rays in Saccharomyces cerevisiae[J]. Dose Response, 2018, 16(3): 294-304.
[35]	Zhang MM, Guo XP, Liu RY, et al. Lipidomics studies on mitochondrial damage of Saccharomyces cerevisiae induced by heavy ion beam radiation[J]. Chin J Anal Chem, 2018, 46(11): 1714-1723. doi: 10.1016/S1872-2040(18)61123-5 URL
[36]	Guo XP, Zhang MM, Gao Y, et al. A genome-wide view of mutations in respiration-deficient mutants of Saccharomyces cerevisiae selected following carbon ion beam irradiation[J]. Appl Microbiol Biotechnol, 2019, 103(4): 1851-1864. doi: 10.1007/s00253-019-09626-0
[37]	Guo XP, Zhang MM, Gao Y, et al. Repair characteristics and time-dependent effects in response to heavy-ion beam irradiation in Saccharomyces cerevisiae: a comparison with X-ray irradiation[J]. Appl Microbiol Biotechnol, 2020, 104(9): 4043-4057. doi: 10.1007/s00253-020-10464-8
[38]	Guo XP, Zhang MM, Gao Y, et al. Quantitative multi-omics analysis of the effects of mitochondrial dysfunction on lipid metabolism in Saccharomyces cerevisiae[J]. Appl Microbiol Biotechnol, 2020, 104(3): 1211-1226. doi: 10.1007/s00253-019-10260-z
[39]	Zhang WW, Li F, Nie L. Integrating multiple ‘omics’ analysis for microbial biology: application and methodologies[J]. Microbiology(Reading), 2010, 156(Pt 2): 287-301.
[40]	Hirano T, Kazama Y, Ishii K, et al. Comprehensive identification of mutations induced by heavy-ion beam irradiation in Arabidopsis thaliana[J]. Plant J, 2015, 82(1): 93-104. doi: 10.1111/tpj.2015.82.issue-1 URL
[41]	Hirano T, Kazama Y, Ohbu S, et al. Molecular nature of mutations induced by high-LET irradiation with argon and carbon ions in Arabidopsis thaliana[J]. Mutat Res, 2012, 735(1/2): 19-31. doi: 10.1016/j.mrfmmm.2012.04.010 URL
[42]	Sage E, Harrison L. Clustered DNA lesion repair in eukaryotes: relevance to mutagenesis and cell survival[J]. Mutat Res Mol Mech Mutagen, 2011, 711(1/2): 123-133.
[43]	Kazama Y, Hirano T, Saito H, et al. Characterization of highly efficient heavy-ion mutagenesis in Arabidopsis thaliana[J]. BMC Plant Biol, 2011, 11: 161. doi: 10.1186/1471-2229-11-161
[44]	Ma LQ, Kazama Y, Hirano T, et al. LET dependence on killing effect and mutagenicity in the model filamentous fungus Neurospora crassa[J]. Int J Radiat Biol, 2018, 94(12): 1125-1133. doi: 10.1080/09553002.2019.1524940 URL
[45]	Morita R, Ichida H, Hayashi Y, et al. Responsible gene analysis of phenotypic mutants revealed the linear energy transfer(LET)-dependent mutation spectrum in rice[J]. Cytologia, 2021, 86(4): 303-309. doi: 10.1508/cytologia.86.303 URL
[46]	Shikazono N, Tanaka A, Kitayama S, et al. LET dependence of lethality in Arabidopsis thaliana irradiated by heavy ions[J]. Radiat Environ Biophys, 2002, 41(2): 159-162. pmid: 12211212
[47]	Hagiwara Y, Oike T, Niimi A, et al. Clustered DNA double-strand break formation and the repair pathway following heavy-ion irradiation[J]. J Radiat Res, 2019, 60(1): 69-79. doi: 10.1093/jrr/rry096 pmid: 30476166
[48]	Win KT, Vegas J, Zhang CY, et al. QTL mapping for downy mildew resistance in cucumber via bulked segregant analysis using next-generation sequencing and conventional methods[J]. Theor Appl Genet, 2017, 130(1): 199-211. doi: 10.1007/s00122-016-2806-z pmid: 27714417
[49]	Kazama Y, Hirano T, Abe T, et al. Chromosomal rearrangement: from induction by heavy-ion irradiation to in vivo engineering by genome editing[J]. Cytologia, 2018, 83(2): 125-128. doi: 10.1508/cytologia.83.125 URL
[50]	Manzoni C, Kia DA, Vandrovcova J, et al. Genome, transcriptome and proteome: the rise of omics data and their integration in biomedical sciences[J]. Brief Bioinform, 2018, 19(2): 286-302. doi: 10.1093/bib/bbw114 pmid: 27881428
[51]	Ozsolak F, Platt AR, Jones DR, et al. Direct RNA sequencing[J]. Nature, 2009, 461(7265): 814-818. doi: 10.1038/nature08390
[52]	Robertson KL, Mostaghim A, Cuomo CA, et al. Adaptation of the black yeast Wangiella dermatitidis to ionizing radiation: molecular and cellular mechanisms[J]. Plos One, 2012, 7(11): e48674. doi: 10.1371/journal.pone.0048674 URL
[53]	Hu W, Li WJ, Chen H, et al. Changes in transcript levels of starch hydrolysis genes and raising citric acid production via carbon ion irradiation mutagenesis of Aspergillus niger[J]. PLoS One, 2017, 12(6): e0180120. doi: 10.1371/journal.pone.0180120 URL
[54]	Kim HI, Nam JY, Cho JY, et al. Next-generation sequencing-based transcriptome analysis of L-lysine-producing Corynebacterium glutamicum ATCC 21300 strain[J]. J Microbiol, 2013, 51(6): 877-880. doi: 10.1007/s12275-013-3236-0 URL
[55]	Sun L, Lu ZL, Li JX, et al. Comparative genomics and transcriptome analysis of Lactobacillus rhamnosus ATCC 11443 and the mutant strain SCT-10-10-60 with enhanced L-lactic acid production capacity[J]. Mol Genet Genomics, 2018, 293(1): 265-276. doi: 10.1007/s00438-017-1379-0
[56]	Kim MW, Lee BR, You S, et al. Transcriptome analysis of wild-type and afsS deletion mutant strains identifies synergistic transcriptional regulator of afsS for a high antibiotic-producing strain of Streptomyces coelicolor A3(2)[J]. Appl Microbiol Biotechnol, 2018, 102(7): 3243-3253. doi: 10.1007/s00253-018-8838-3
[57]	禹伟, 高教琪, 周雍进. 蛋白质组学和代谢组学在微生物代谢工程中的应用[J]. 色谱, 2019, 37(8): 798-805. doi: 10.3724/SP.J.1123.2019.04026
	Yu W, Gao JQ, Zhou YJ. Application of proteomics and metabolomics in microbial metabolic engineering[J]. Chin J Chromatogr, 2019, 37(8): 798-805. doi: 10.3724/SP.J.1123.2019.04026
[58]	Haqqani AS, Kelly JF, Stanimirovic DB. Quantitative protein profiling by mass spectrometry using label-free proteomics[J]. Methods Mol Biol, 2008, 439: 241-256. doi: 10.1007/978-1-59745-188-8_17 pmid: 18370108
[59]	Yoon M, Choi JI, Kim GH, et al. Proteomic analysis of Spirogyra varians mutant with high starch content and growth rate induced by gamma irradiation[J]. Bioprocess Biosyst Eng, 2013, 36(6): 765-774. doi: 10.1007/s00449-013-0902-x URL
[60]	Park EJ, Choi JI. Resistance and proteomic response of microalgae to ionizing irradiation[J]. Biotechnol Bioprocess Eng, 2018, 23(6): 704-709. doi: 10.1007/s12257-018-0468-1
[61]	王洁. 碳离子辐照对绿藻光合系统的影响及诱变机理研究[D]. 北京: 中国科学院研究生院(近代物理研究所), 2016.
	Wang J. The effects and mechanisms on photosynthesis system of green algae after carbon ions irradiation[D]. Beijing: Institute of Physics, Chinese Academy of Sciences, 2016.
[62]	Wang Y, Guan H, Xie DF, et al. Proteomic analysis implicates dominant alterations of RNA metabolism and the proteasome pathway in the cellular response to carbon-ion irradiation[J]. PLoS One, 2016, 11(10): e0163896. doi: 10.1371/journal.pone.0163896 URL
[63]	Fan PC, Zhang Y, Wang Y, et al. Quantitative proteomics reveals mitochondrial respiratory chain as a dominant target for carbon ion radiation: delayed reactive oxygen species generation caused DNA damage[J]. Free Radic Biol Med, 2019, 130: 436-445. e13. doi: 10.1016/j.freeradbiomed.2018.10.449 URL
[64]	Nitta N, Sugimura T, Isozaki A, et al. Intelligent image-activated cell sorting[J]. Cell, 2018, 175(1): 266-276. doi: S0092-8674(18)31044-4 pmid: 30166209
[65]	Su PR, You L, Beerens C, et al. Microscopy-based single-cell proteomic profiling reveals heterogeneity in DNA damage response dynamics[J]. Cell Rep Methods, 2022, 2(6): 100237.
[66]	Raleigh DR, Haas-Kogan DA. Molecular targets and mechanisms of radiosensitization using DNA damage response pathways[J]. Future Oncol, 2013, 9(2): 219-233. doi: 10.2217/fon.12.185 pmid: 23414472
[67]	Ota S, Matsuda T, Takeshita T, et al. Phenotypic spectrum of Parachlorella kessleri(Chlorophyta)mutants produced by heavy-ion irradiation[J]. Bioresour Technol, 2013, 149: 432-438. doi: 10.1016/j.biortech.2013.09.079 URL
[68]	Ma YB, Wang ZY, Zhu M, et al. Increased lipid productivity and TAG content in Nannochloropsis by heavy-ion irradiation mutagenesis[J]. Bioresour Technol, 2013, 136: 360-367. doi: 10.1016/j.biortech.2013.03.020 URL
[69]	Li B, Han C, Liu YY, et al. Effect of heavy ion ¹²C⁶⁺ radiation on lipid constitution in the rat brain[J]. Molecules, 2020, 25(16): 3762. doi: 10.3390/molecules25163762 URL
[70]	Pannkuk EL, Laiakis EC, Mak TD, et al. A lipidomic and metabolomic serum signature from nonhuman Primates exposed to ionizing radiation[J]. Metabolomics, 2016, 12(5): 80. doi: 10.1007/s11306-016-1010-0 URL
[71]	Pannkuk EL, Fornace AJ Jr, Laiakis EC. Metabolomic applications in radiation biodosimetry: exploring radiation effects through small molecules[J]. Int J Radiat Biol, 2017, 93(10): 1151-1176. doi: 10.1080/09553002.2016.1269218 pmid: 28067089
[72]	Hu W, Li W, Chen J. Recent advances of microbial breeding via heavy-ion mutagenesis at IMP[J]. Lett Appl Microbiol, 2017, 65(4): 274-280. doi: 10.1111/lam.12780 pmid: 28741678
[73]	Satoh K, Oono Y. Studies on application of ion beam breeding to industrial microorganisms at TIARA[J]. QuBS, 2019, 3(2): 11. doi: 10.3390/qubs3020011 URL
[74]	贾蓉, 苏锋涛, 胡步荣. 重离子的辐射生物效应及其在生命科学中的应用[J]. 生物技术通报, 2018, 34(1): 67-78. doi: 10.13560/j.cnki.biotech.bull.1985.2017-0735
	Jia R, Su FT, Hu BR. The biological effects induced by heavy ion radiation and its application in life science[J]. Biotechnol Bull, 2018, 34(1): 67-78. doi: 10.13560/j.cnki.biotech.bull.1985.2017-0735

微生物菌株 Microorganism	离子类型 Ion beam	能量Energy /（MeV·u^-1）	突变结果 Mutation results	参考文献 Reference
链霉菌Streptomyces fungicidicus SG-01	¹²C⁶⁺	80	恩拉霉素产量增加43%	[5]
高山被孢霉菌Mortierella alpine SD003	¹²C⁶⁺	80	花生四烯酸产量达到 5.26 g/L	[7]
小花棘豆内生真菌Alternaria oxytropis UO1 酪丁酸梭菌Clostridium tyrobutyricum	¹²C⁶⁺ ¹²C⁶⁺	80 80	生物碱苦马豆素产量提高14.84% pH耐受性达到4.5和5.0	[10] [17]
谷氨酸棒状杆菌Corynebacterium Glutamicum GM006	¹²C⁶⁺	80	谷氨酸产量提高10.09%	[18]
丙酮丁醇梭菌C. acetobutylicum CICC 8012	¹²C⁶⁺	80	丁醇产量增加33%，丁醇抗性达到19 g/L	[19]
节杆菌Arthrobacter strain C1	¹²C⁶⁺	76.37	生物量达到129.84%，Cd²⁺抗性提高至100 mg/L	[20]
烟曲霉A. fumigatus MS13.1	¹²C⁶⁺	80	滤纸酶活性和葡萄糖苷酶活性分别提高 40.3%和15.1%	[21]
斜生栅藻Scenedesmus obliqnus SO120G	¹²C⁶⁺	80	脂质产量提高2.4倍	[22]
杜氏盐藻Dunaliella salina DS240G-1	¹²C⁶⁺	80	β-胡萝卜素含量增加21%	[23]

微生物菌株 Microorganism	离子类型 Ion beam	能量Energy /（MeV·u^-1）	突变结果 Mutation results	参考文献 Reference
链霉菌Streptomyces fungicidicus SG-01	¹²C⁶⁺	80	恩拉霉素产量增加43%	[5]
高山被孢霉菌Mortierella alpine SD003	¹²C⁶⁺	80	花生四烯酸产量达到 5.26 g/L	[7]
小花棘豆内生真菌Alternaria oxytropis UO1 酪丁酸梭菌Clostridium tyrobutyricum	¹²C⁶⁺ ¹²C⁶⁺	80 80	生物碱苦马豆素产量提高14.84% pH耐受性达到4.5和5.0	[10] [17]
谷氨酸棒状杆菌Corynebacterium Glutamicum GM006	¹²C⁶⁺	80	谷氨酸产量提高10.09%	[18]
丙酮丁醇梭菌C. acetobutylicum CICC 8012	¹²C⁶⁺	80	丁醇产量增加33%，丁醇抗性达到19 g/L	[19]
节杆菌Arthrobacter strain C1	¹²C⁶⁺	76.37	生物量达到129.84%，Cd²⁺抗性提高至100 mg/L	[20]
烟曲霉A. fumigatus MS13.1	¹²C⁶⁺	80	滤纸酶活性和葡萄糖苷酶活性分别提高 40.3%和15.1%	[21]
斜生栅藻Scenedesmus obliqnus SO120G	¹²C⁶⁺	80	脂质产量提高2.4倍	[22]
杜氏盐藻Dunaliella salina DS240G-1	¹²C⁶⁺	80	β-胡萝卜素含量增加21%	[23]