基于Bt毒素的杀虫蛋白理性设计与创新应用策略

doi:10.3864/j.issn.0578-1752.2024.01.008

中国农业科学 ›› 2024, Vol. 57 ›› Issue (1): 96-125.doi: 10.3864/j.issn.0578-1752.2024.01.008

基于Bt毒素的杀虫蛋白理性设计与创新应用策略

徐重新¹^,²(), 金嘉凤¹^,², 孙晓明¹, 沈成¹^,³, 张霄¹, 陈澄宇¹, 刘贤金¹, 刘媛¹^,²()

¹ 江苏省农业科学院农产品质量安全与营养研究所/省部共建国家重点实验室培育基地-江苏省食品质量安全重点实验室，南京 210014
² 江苏大学食品与生物工程学院，江苏镇江 212013
³ 南京农业大学植物保护学院，南京 210023

收稿日期:2023-07-28 接受日期:2023-09-21 出版日期:2024-01-01 发布日期:2024-01-10
通信作者:
徐重新，E-mail：hhxyxcx@163.com。

刘媛，E-mail：liuyuan@jaas.ac.cn
联系方式: 徐重新，E-mail：hhxyxcx@163.com。
基金资助:
江苏省自然科学基金面上项目(BK20231384); 国家自然科学基金重点项目(31630061); 江苏省农业自主创新项目(CX(22)1009)

Rational Design and Innovative Application Strategy for the Insecticidal Protein Based on Bt Toxin

XU ChongXin¹^,²(), JIN JiaFeng¹^,², SUN XiaoMing¹, SHEN Cheng¹^,³, ZHANG Xiao¹, CHEN ChengYu¹, LIU XianJin¹, LIU Yuan¹^,²()

¹ Institute of Food Safety and Nutrition, Jiangsu Academy of Agricultural Sciences/Jiangsu Key Laboratory of Food Quality and Safety-Laboratory for Food Quality and Safety State Key Laboratory Cultivation Base of Ministry of Science and Technology, Nanjing 210014
² School of Food and Biological Engineering, Jiangsu University, Zhenjiang 212013, Jiangsu
³ College of Plant Protection, Nanjing Agricultural University, Nanjing 210023

Received:2023-07-28 Accepted:2023-09-21 Published:2024-01-01 Online:2024-01-10

摘要/Abstract

摘要：

Bt毒素是源于苏云金芽孢杆菌（Bacillus thuringiensis）的具有特殊杀虫功能的大分子蛋白，其制剂和转基因作物已广泛用于害虫防治，产生了巨大的经济和社会生态效益。围绕Bt毒素挖掘和提升其应用价值是持续研究的热点，特别是随着Bt毒素结构功能和作用机制日趋明晰，为其功能修饰和创新应用创造了条件，相关研究蓬勃发展，成效显著。大量研究表明，采用定点突变、结构域替换或融合以及抗独特型抗体模拟等策略，是理性设计活性更高、稳定性更强、杀虫谱更广、非靶标生物安全性更高甚至是可用于害虫抗药性治理的有别于母体Bt毒素的突变体、结构杂合体乃至功能效应物抗体等新型杀虫蛋白的有效手段；此外，采用催化毒素活化、驱动毒素靶向受体结合、促进毒素表达以及同源或异源杀虫材料复配或共表达的协同促效等创新增效策略，也是助推Bt毒素应用价值的重要手段。本文总结了Bt毒素结构功能和作用机制，梳理了基于Bt毒素功能修饰的突变体、结构杂合体以及功能效应物抗体等新型杀虫蛋白理性设计和基于Bt毒素功能增效的创新应用策略等相关研究进展，并结合作者团队在模拟Bt毒素杀虫功能效应物抗体靶向设计研发方面的最新成果，探讨了基于Bt毒素的杀虫蛋白理性设计与创新应用策略未来发展动向及潜在可行捷径，为相关研究提供较为全面的最新有价值的文献资料和启发思路。

关键词: Bt毒素, 苏云金芽孢杆菌, 杀虫蛋白, 定点突变, 抗独特型抗体, 蛋白融合表达, 杀虫增效物

Abstract:

Bt toxin is a macromolecular protein derived from Bacillus thuringiensis with special insecticidal function. Its preparation and transgenic crops have been widely used in pest control, and have produced huge economic and social ecological benefits. Exploiting and improving the application value of Bt toxin is a hot spot of continuous research. In particular, as the structure and function of Bt toxin and its mechanism of action appear clearer, it has created conditions for its functional modification and innovative application. As a result, the related research has flourished and achieved remarkable results. A large number of studies have shown that strategies such as site directed mutagenesis, domain replacement or fusion, and anti-idiotype antibody simulation are effective means to rationally design novel insecticidal proteins with higher activity, greater stability, wider insecticidal spectrum and higher non-target biosecurity. Those novel insecticidal proteins are different from parent Bt toxins, of which are mutants, structural heterozygotes and even functional effector antibodies. In addition, it is also an important approach to promote the application value of Bt toxin by use of innovative synergistic strategies such as catalytic toxin activation, driving toxin-targeted receptor binding, promoting toxin expression and the synergistic effect of combination or co-expression of homologous or heterologous insecticidal materials. This paper summarizes the structure and function of Bt toxin and its mechanism of action. It also reviews the research progress in rational design of novel insecticidal proteins such as mutants, structural heterozygotes and functional effector antibodies based on Bt toxin function modification, and innovative application strategies based on Bt toxin function enhancement. The future development trend and potential shortcut of rational design and innovative application strategy for insecticidal protein based on Bt toxin were discussed. Furthermore, the author’s team combined it with the latest achievements in targeting design and development of the insecticidal function effector antibodies simulating Bt toxin. This paper is expected to provide more comprehensive and valuable literature information and enlighten ideas for the related research based on Bt toxin.

Key words: Bt toxin, Bacillus thuringiensis, insecticidal protein, site-directed mutagenesis, anti-idiotype antibody, protein fusion expression, insecticidal synergist

徐重新, 金嘉凤, 孙晓明, 沈成, 张霄, 陈澄宇, 刘贤金, 刘媛. 基于Bt毒素的杀虫蛋白理性设计与创新应用策略[J]. 中国农业科学, 2024, 57(1): 96-125.

XU ChongXin, JIN JiaFeng, SUN XiaoMing, SHEN Cheng, ZHANG Xiao, CHEN ChengYu, LIU XianJin, LIU Yuan. Rational Design and Innovative Application Strategy for the Insecticidal Protein Based on Bt Toxin[J]. Scientia Agricultura Sinica, 2024, 57(1): 96-125.

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链接本文: https://www.chinaagrisci.com/CN/10.3864/j.issn.0578-1752.2024.01.008

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图/表 4

表1

表2

基于Bt毒素的突变体理性设计实例"

供试模板 Tested template	改造位点 Modification site	实施效果 Implementation effect	参考文献 Reference
Cry1Aa	Domain I α4—α5区域153位点氨基酸Y突变为C（Y153C）The amino acid Y at site 153 in Domain I α4-α5 was mutated to C (Y153C)	突变体对烟草天蛾的肠道损伤较原Cry1Aa显著提升The intestinal damage of the mutant to M. sexta was significantly higher than that of the original Cry1Aa	[48]
	Domain II-Loop 2区域氨基酸“RRIILGSGPNNQE”整体突变为人源抗体重链CDR-H3肽段 “GARGDPDFDHSTSYYLDYC” The amino acids “RRIILGSGPNNQE” in Domain II-Loop 2 were mutated to “GARGDPDFDHSTSYYLDYC”, a heavy chain CDR-H3 peptide of human antibody	突变体对埃及伊蚊（LC₅₀为9.1 μg·mL^-1）的致死毒力较原Cry1Aa（LC₅₀>20 μg·mL^-1）提高超过2.2倍；对非靶标家蚕的致死率较原Cry1Aa显著降低The lethal virulence of the mutant against A. aegypti (LC₅₀was 9.1 μg·mL^-1) was more than 2.2-fold higher than that of the original Cry1Aa (LC₅₀>20 μg·mL^-1). The lethality rate of the mutant to non-target B. mori was significantly lower than that of original Cry1Aa	[54]
	Domain II-Loop 2区域³⁷¹LGSG³⁷¹氨基酸突变³⁷¹WGLA³⁷⁴The amino acids ³⁷¹LGSG³⁷¹ in Domain II-Loop 2 were mutated to ³⁷¹WGLA³⁷⁴	突变体对家蚕（LC₅₀为0.752 μg·g^-1）的致死毒力较原Cry1Aa （LC₅₀为0.864 μg·g^-1）提高15% The lethal virulence of the mutant to B. mori (LC₅₀was 0.752 μg·g^-1) was 15% higher than that of the original Cry1Aa (LC₅₀was 0.864 μg·g^-1)	[4]
	Domain II-Loop 3区域⁴⁴⁰AA⁴⁴¹氨基酸突变为⁴⁴⁰PR⁴⁴¹The amino acids ⁴⁴⁰AA⁴⁴¹ in Domain II-Loop 3 were mutated to ⁴⁴⁰PR⁴⁴¹	突变体对家蚕（LC₅₀为0.398 μg·g^-1）的致死毒力较原Cry1Aa（LC₅₀为0.996 μg·g^-1）提高2.5倍The lethal virulence of the mutant to B. mori (LC₅₀was 0.398 μg·g^-1) was 2.5-fold higher than that of the original Cry1Aa (LC₅₀was 0.996 μg·g^-1)	[55]
Cry1Ab	Domain II Loop2区域282位点氨基酸A、283位点氨基酸L和372位点氨基酸N分别突变为G（A282G）、S（L283S）和A（N372A）The amino acids A at 282 site, L at 283 site and N at 372 site in Domain II Loop2 were mutated to G (A282G), S (L283S) and A (N372A), respectively	突变体对苹果毒蛾（LC₅₀为8 ng·cm^-2）的致死毒力较原Cry1Ab（LC₅₀为290 μg·cm^-2）提高36.25倍The lethal virulence of the mutant to Lymantria dispar (LC₅₀was 8 ng·cm^-2) was 36.25-fold higher than that of the original Cry1Ab (LC₅₀was 290 μg·cm^-2)	[50]
	Domain II Loop2 ³³⁵RRPFNIGINNQ³⁴⁵突变为褐飞虱肠道结合肽GBPs-P2S（CLMSSQAAC）The amino acids ³³⁵RRPFNIGINNQ³⁴⁵ in Domain II Loop2 were mutated to Nilaparvata lugens gut-binding peptide GBPs-P2S (CLMSSQAAC)	突变体对褐飞虱（LC₅₀为21.54 μg·mL^-1）的致死毒力较原Cry1Ab（LC₅₀为189.83 μg·mL^-1）提高9倍The lethal virulence of the mutant to N. lugens (LC₅₀was 21.54 μg·mL^-1) was 9-fold higher than that of the original Cry1Ab (LC₅₀was 189.83 μg·mL^-1)	[51]
	Domain III β16区域514位点氨基酸N突变为A（N514A）The amino acid N at 514 site in Domain III β16 was mutated to A (N514A)	突变体对草地贪夜蛾（LC₅₀为26.4 μg·cm^-2）的致死毒力较原Cry1Ab（LC₅₀为468 μg·cm^-2）提高18倍The lethal virulence of the mutant to S. frugiperda (LC₅₀was 26.4 μg·cm^-2) was 18-fold higher than that of the original Cry1Ab (LC₅₀was 468 μg·cm^-2)	[56]
	Domain III β-22区域587位点氨基酸S突变为A（S587A）The amino acid S at 587 site in Domain III β-22 was mutated to A (S587A)	突变体对草地贪夜蛾（LC₅₀为44 ng·cm^-2）的致死毒力较原Cry1Ab（LC₅₀>5000 ng·cm^-2）显著增强The lethal virulence of the mutant to S. frugiperda (LC₅₀was 44 ng·cm^-2) was significantly higher than that of the original Cry1Ab (LC₅₀>5000 ng·cm^-2)	[57]
Cry1Ac	Domain III β16—β17连接区域524位点氨基酸T突变为N（T524N）The amino acid T at 524 site in Domain III β16-β17 connection area was mutated to N (T524N)	突变体对甜菜夜蛾（LC₅₀为9.6 μg·mL^-1）的致死毒力较原Cry1Ac（LC₅₀为14.1 μg·mL^-1）提升1.4倍The lethal virulence of the mutant to S. exigua (LC₅₀was 9.6 μg·mL^-1) was 1.4-fold higher than that of the original Cry1Ac (LC₅₀was 14.1 μg·mL^-1)	[72]
	Domain III β18—β19连接区域544位点氨基酸W突变为F（W544F）The amino acid W at 544 site in Domain III β18-β19 connection area was mutated to F (W544F)	突变体抗虫活性保持不变，但对紫外线的稳定性显著增强The insecticidal activity of the mutant remained unchanged, but its stability to UV radiation was significantly enhanced	[12]
	Domain III β18—β19连接区域546位点氨基酸N突变为A（N546A）The amino acid N at 546 site in Domain III β18-β19 connection area was mutated to A (N546A)	突变体对棉铃虫（LC₅₀为1.67 μg·mL^-1）的致死毒力较原Cry1Ac（LC₅₀为2.98 μg·mL^-1）提高1.78倍The lethal virulence of the mutant to H. armigera (LC₅₀was 1.67 μg·mL^-1) was 1.78-fold higher than that of the original Cry1Ac (LC₅₀was 2.98 μg·mL^-1)	[58]
	Domain III β20—β21连接区域585位点氨基酸I突变为A（I585A）The amino acid I at 585 site in Domain III β20-β21 connection area was mutated to A (I585A)	突变体对棉铃虫（LC₅₀为1.47 μg·mL^-1）的致死毒力较原Cry1Ac（LC₅₀为2.78 μg·mL^-1）提高1.89倍The lethal virulence of the mutant to H. armigera (LC₅₀was 1.47 μg·mL^-1) was 1.89-fold higher than that of the original Cry1Ac (LC₅₀为2.78 μg·mL^-1)	[59]
Cry1Ai	Domain II Loop2（RIILGSGPNNQE）、Loop3 （TMLSQAAGAVYTL）分别突变为Cry1Ah的Loop2（RPFNIGINNQQ）和Loop3（SMFRSGSSSSVSII）The amino acids of Domain II Loop2 (RIILGSGPNNQE) and Loop3 (TMLSQAAGAVYTL) were mutated to Cry1Ah Loop2 (RPFNIGINNQQ) and Loop3 (SMFRSGSSSSVSII), respectively	突变体对棉铃虫（LC₅₀为8.6 μg·mL^-1）的致死毒力较原Cry1Ai（LC₅₀>500 μg·mL^-1）显著提升The lethal virulence of the mutant to H. armigera (LC₅₀was 8.6 μg·mL^-1) was significantly higher than that of the original Cry1Ai (LC₅₀>500 μg·mL^-1)	[52]
Cry1Ca	Domain III区域⁵⁴¹STGV⁵⁴⁴突变为⁵⁴¹AAAA⁵⁴⁴The amino acids ⁵⁴¹STGV⁵⁴⁴ in Domain III were mutated to ⁵⁴¹AAAA⁵⁴⁴	突变体对烟草天蛾（LC₅₀为80 ng·cm^-2）的致死毒力较原Cry1Ca（LC₅₀为123 ng·cm^-2）提高43% The lethal virulence of the mutant to M. sexta (LC₅₀was 80 ng·cm^-2) was 43% higher than that of the original Cry1Ca (LC₅₀was 123 ng·cm^-2)	[73]
Cry1Fa	Domain III β16区域507位点氨基酸N突变为A（N507A）The amino acid N at 507 site in Domain III β16 was mutated to A (N507A)	突变体对草地贪夜蛾（LC₅₀为28.7 ng·cm^-2）的致死毒力较原Cry1Fa（LC₅₀为171 ng·cm^-2）提高5.95倍The lethal virulence of the mutant to S. frugiperda (LC₅₀was 28.7 ng·cm^-2) was 5.95-fold higher than that of the original Cry1Fa (LC₅₀was 171 ng·cm^-2)	[56]
Cry2Aa	Domain I α2—α3区域63、64位点氨基酸K分别突变为F（K63F）和P（K64P）The amino acids K at 63 and 64 sites in Domain I α2-α3 were mutated to F (K63F) and P (K64P), respectively	突变体对斜纹夜蛾、小地老虎和棉铃虫（LC₅₀分别为6.09、72.37和51.33 ng·mL^-1）的致死毒力较原Cry2Aa（LC₅₀分别为40.09、299.88和251.33 ng·mL^-1）提高4.1—6.6倍The lethal virulence of the mutant to Spodoptera litura, Agrotis ypsilon and H. armigera (LC₅₀was 6.09, 72.37 and 51.33 ng·mL^-1, respectively) was 4.1-6.6 folds higher than that of the original Cry2Aa (LC₅₀was 40.09, 299.88 and 251.33 ng·mL^-1, respectively)	[43]
Cry2Ab	Domain I α3—α4区域144位点氨基酸L突变为A（L144A）The amino acid L at 144 site in Domain I α3-α4 was mutated to A (L144A)	突变体对小菜蛾（LD₅₀为1.579 μg·cm^-2）的致死毒力较原Cry2Ab（LD₅₀为1.801 μg·cm^-2）提高1.14倍The lethal virulence of the mutant to P. xylostella (LD₅₀was 1.579 μg·cm^-2) was 1.14- fold higher than that of the original Cry2Ab (LD₅₀was 1.801 μg·cm^-2)	[47]
Cry2Ah	Domain II β4—β5之间Loop2区域354位点氨基酸V突变为SP（V354SP）The amino acid V at Loop2 region 354 site in Domain II β4-β5 was mutated to SP (V354SP)	突变体对棉铃虫（EC₅₀为1.63 μg·mL^-1）的致死毒力较原Cry2Ah（EC₅₀为8.7 μg·mL^-1）提高5.3倍The lethal virulence of the mutant to H. armigera (EC₅₀was 1.63 μg·mL^-1) was 5.3-fold higher than that of the original Cry2Ah (EC₅₀was 8.7 μg·mL^-1)	[53]
Cry3Aa	Domain I α3—α4之间的连接区域¹⁵³NPVSSRNPHS¹⁶²突变为¹⁵³NPAPPF-PHS¹⁶²The amino acids ¹⁵³NPVSSRNPHS¹⁶² in Domain I α3-α4 connection area were mutated to ¹⁵³NPAPPF-PHS¹⁶²	突变体对玉米根虫的致死率（93%）较原Cry3Aa（34%）提高2.74倍The lethality rate of the mutant (93%) to D. virgifera was 2.74-fold higher than that of the original Cry3Aa (34%)	[45]
	Domain I区域65、70、231位点氨基酸K以及Domain II区域468位点氨基酸K和Domain III区域596位点氨基酸K均突变为A The amino acids K at 65, 70 and 231 sites in Domain I, 468 site in Domain II and 596 site in Domain III were mutated to A	突变体对松褐天牛（LC₅₀为12.3 μg·mL^-1）的致死毒力较原Cry3Aa（LC₅₀为116.8 μg·mL^-1）提高9.5倍The lethal virulence of the mutant to Monochamus alternatus (LC₅₀was 12.3 μg·mL^-1) was 9.5-fold higher than that of the original Cry3Aa (LC₅₀was 116.8 μg·mL^-1)	[74]
	Domain II Loop1区域345位点氨基酸R、350和351位点氨基酸Y分别突变为A（R345A）、F（Y350F）和F（Y351F）The amino acids R at 345 site, Y at 350 and 351 sites in Domain II Loop1 were mutated to A (R345A), F (Y350F) and F (Y351F), respectively	突变体对黄粉虫（LD₅₀为1.0 μg）的致死毒力较原Cry3Aa（LD₅₀为11.4 μg）提高11.4倍The lethal virulence of the mutant to Tenebrio molitor (LD₅₀was 1.0 μg) was 11.4-fold higher than that of the original Cry3Aa (LD₅₀was 11.4 μg)	[75]
Cry4Aa	Domain I α2—α3区域⁶⁷SG⁶⁸突变为⁶⁷SFRRG⁷¹、²³⁴NR²³⁵突变为²³⁴NFRR²³⁷The amino acids ⁶⁷SG⁶⁸ and ²³⁴NR²³⁵in Domain I α2-α3 were mutated to ⁶⁷SFRRG⁷¹and ²³⁴NFRR²³⁷, respectively	突变体对豌豆蚜的致死率（51.1%）较原Cry4Aa（17.8%）提高2.87倍The lethality rate of the mutant (51.1%) to A. pisum was 2.87-fold higher than that of the original Cry4Aa (17.8%)	[44]
Cry8Ca	Domain II区域439位点氨基酸Q突变为P（Q439P）、Domain III区域884位点氨基酸E突变为G（E884G）The amino acids Q at 439 site in Domain II and E at 884 site in Domain III were mutated to P (Q439P) and G (E884G), respectively	突变体对铜绿鳃金龟（LC₅₀为0.22334×10⁸ CFU/g）的致死毒力较原Cry8Ca（LC₅₀为0.9583×10⁸ CFU/g）提高4.3倍The lethal virulence of the mutant to Anomala corpulenta (LC₅₀was 0.22334×10⁸ CFU/g) was 4.3-fold higher than that of the original Cry8Ca (LC₅₀was 0.9583×10⁸ CFU/g)	[76]
Cry8Ka	Domain I α3区域82位点氨基酸R突变为Q（R82Q）；Domain II Loop区域260位点氨基酸Y突变为C（Y260C）、321位点氨基酸P突变为A（P321A）；Domain III区域508位点氨基酸R突变为G（R508G）、538位点氨基酸K突变为E（K538E）、594位点氨基酸E突变为N（E594N）The amino acids R at 82 site in Domain I α3, Y at 260 and P at 321 sites in Domain II Loop, and R at 508, K at 538 and E at 594 sites in Domain III were mutated to Q (R82Q), C (Y260C), A (P321A), G (R508G), E (K538E) and N (E594N), respectively	突变体对棉铃象甲（LC₅₀为2.83 μg·mL^-1）的致死毒力较原Cry8Ka（LC₅₀为8.93 μg·mL^-1）提高3.15倍The lethal virulence of the mutant to Anthonomus grandis (LC₅₀为2.83 μg·mL^-1) was 3.15-fold higher than that of the original Cry8Ka (LC₅₀为8.93 μg·mL^-1)	[46]
Cry19Aa	Domain II Loop 1 ³⁵⁵SYWT³⁵⁸突变为³⁵⁵YQDLR³⁵⁹，同时切掉Loop 2的⁴¹⁴YPWGD⁴¹⁸The amino acids ³⁵⁵SYWT³⁵⁸in Domain II Loop 1 were mutated to³⁵⁵YQDLR³⁵⁹, and at the same time the amino acids ⁴¹⁴YPWGD⁴¹⁸ in Loop 2 were deleted	突变体对埃及伊蚊（LC₅₀为3.3 ng·mL^-1）的致死毒力较原Cry19Aa（LC₅₀为1.4×10⁵ng·mL^-1）提高42000倍The lethal virulence of the mutant to A. aegypti (LC₅₀was 3.3 ng·mL^-1) was 42000-fold higher than that of the original Cry19Aa (LC₅₀was 1.4×10⁵ng·mL^-1)	[49]
Cry41-related	48位点氨基酸G、59位点氨基酸I、364位点氨基酸K、367和377位点氨基酸Q、378位点氨基酸Y、400位点氨基酸S分别突变为Y（G48Y）、A（I59A）、R（K364R）、K（Q367K）、K（Q377K）、K（Y378K）、Y（S400Y）The amino acids G at 48, I at 59, K at 364, Q at 367 and 377, Y at 378 and S at 400 sites were mutated to Y (G48Y), A (I59A), R (K364R), K (Q367K), K (Q377K), K (Y378K) and Y (S400Y), respectively	突变体对桃蚜（LC₅₀为19.144 μg·mL^-1）的致死毒力较原Cry41-type（LC₅₀为32.7 μg·mL^-1）提高1.71倍The lethal virulence of the mutant to Myzus persicae (LC₅₀was 19.144 μg·mL^-1) was 1.71-fold higher than that of the original Cry41-type (LC₅₀was 32.7 μg·mL^-1)	[77]
Cry51Aa	46位点氨基酸F、54位点氨基酸Y、95位点氨基酸S、147位点氨基酸F、167位点氨基酸S、219位点氨基酸P、239位点氨基酸N、251位点氨基酸V分别突变为S（F46S）、H（Y54H）、A（S95A）、A（F147A）、R（S167R）、R（P219R）、A（N239A）、A（V251A） The amino acids F at 46, Y at 54, S at 95, F at 147, S at 167, P at 219, N at 239 and V at 251 sites were mutated to S (F46S), H (Y54H), A (S95A), A (F147A), R (S167R), R (P219R), A (N239A) and A (V251A), respectively	突变体对豆荚草盲蝽（LC₅₀为0.3 μg·mL^-1）和美洲牧草盲蝽（LC₅₀为0.85 μg·mL^-1）的致死毒力较原Cry51Aa（LC₅₀分别为73和>223 μg·mL^-1）提高243和>262倍The lethal virulence of the mutant to Lygus hesperus (LC₅₀was 0.3 μg·mL^-1) and Lygus lineolaris (LC₅₀was 0.85 μg·mL^-1) was 243 and >262 folds higher than that of the original Cry51Aa (LC₅₀was 73 and >223 μg·mL^-1), respectively	[78]
Cyt1Aa	Loop6-αE区域204位点氨基酸E突变为A（E204A）The amino acid E at 204 site in Loop6-αE was mutated to A (E204A)	突变体对埃及伊蚊（LC₅₀为103.9 ng·mL^-1）的致死毒力较原Cyt1Aa（LC₅₀为952.5 ng·mL^-1）提高9.17倍The lethal virulence of the mutant to A. aegypti (LC₅₀was 103.9 ng·mL^-1) was 9.17-fold higher than that of the original Cyt1Aa (LC₅₀was 952.5 ng·mL^-1)	[63]
Cyt1Aa	Loop6/7/9同时突变为Cry1Ab Domain II Loop3（FRSGFSNSSVSI）The amino acids of Loop6/7/9 were mutated to Cry1Ab Domain II Loop3 (FRSGFSNSSVSI)	突变体对烟草天蛾和小菜蛾的致死率较原Cyt1Aa提高60%—80% The lethality rate of the mutant to M. sexta and P. xylostella was 60%-80% higher than that of the original Cyt1Aa	[64]
Cyt2Aa	Loop4 ¹⁷⁷SLSAHN¹⁸¹突变为豌豆蚜肠道结合肽GBP3.1（TCSKKYPRSPCM）The amino acids of Loop4 ¹⁷⁷SLSAHN¹⁸¹were mutated to A. pisum intestinal binding peptide GBP3.1 (TCSKKYPRSPCM)	突变体对豌豆蚜和桃蚜（LC₅₀分别为0.18和11.9 μg·mL^-1）的致死毒力较原Cyt2Aa（LC₅₀分别为0.37和>150 μg·mL^-1）显著增强The lethal virulence of the mutant to A. pisum and M. persicae (LC₅₀was 0.18 and 11.9 μg·mL^-1) was significantly higher than that of the original Cyt2Aa (LC₅₀was 0.37 and >150 μg·mL^-1)	[65]
Vip3Aa	Domain I和Domain II之间的Loop区域¹⁹³SS¹⁹⁴突变为¹⁹³RA¹⁹⁴、197位点氨基酸K突变为RA（K197RA）The amino acids ¹⁹³SS¹⁹⁴in Loop area between Domain I and Domain II were mutated to ¹⁹³RA¹⁹⁴, and K at 197 site was mutated to RA (K197RA)	突变体对草地贪夜蛾和棉铃虫（LC₅₀分别为32.94和148.2 ng·cm^-2）的致死毒力较原Vip3Aa（LC₅₀分别为56.76和270.1 ng·cm^-2）显著增强The lethal virulence of the mutant to S. frugiperda and H. armigera (LC₅₀was 32.94 and 148.2 ng·cm^-2) was significantly higher than that of the original Vip3Aa (LC₅₀was 56.76 and 270.1 ng·cm^-2)	[79]
	Domain IV区域543位点氨基酸S、544位点氨基酸I和Domain V区域627位点氨基酸E分别突变为N（S543N）、L（I544L）和A（E627A）The amino acids S at 543 and I at 544 sites in Domain IV, and E at 627 site in Domain V were mutated to N (S543N), L (I544L) and A (E627A), respectively	突变体对草地贪夜蛾（LC₅₀为0.3 μg·g^-1）的致死毒力较原Vip3Aa（LC₅₀为2.2 μg·g^-1）提高7.3倍The lethal virulence of the mutant to S. frugiperda (LC₅₀was 0.3 μg·g^-1) was 7.3-fold higher than that of the original Vip3Aa (LC₅₀was 2.2 μg·g^-1)	[68]
	Domain V区域686位点氨基酸S突变为R（S686R）The amino acid S at 686 site in Domain V was mutated to R (S686R)	突变体对甜菜夜蛾（LC₅₀为2.05 μg·mL^-1）的致死毒力较原Vip3Aa（LC₅₀为18.4 μg·mL^-1）提高8.98倍The lethal virulence of the mutant to S. exigua (LC₅₀was 2.05 μg·mL^-1) was 8.98-fold higher than that of the original Vip3Aa (LC₅₀was18.4 μg·mL^-1)	[69]
	Domain V区域776位点氨基酸N突变为Y（N776Y）The amino acid N at 776 site in Domain V was mutated to Y (N776Y)	突变体对甜菜夜蛾（LC₅₀为110 ng·cm^-2）的致死毒力较原Vip3Aa（LC₅₀为250 ng·cm^-2）提高2.27倍；且热稳定性显著增强The lethal virulence of the mutant to S. exigua (LC₅₀为was 110 ng·cm^-2) was 2.27-fold higher than that of the original Vip3Aa (LC₅₀was 250 ng·cm^-2), and the thermal stability was significantly enhanced	[70]
Vip3Af	Domain II区域250位点氨基酸K突变为A（K250A） The amino acid K at 250 site in Domain II was mutated to A (K250A)	突变体对草地贪夜蛾的致死率（91%）较原Vip3Af（72%）提高19% The lethality rate of the mutant (91%) to S. frugiperda was 19% higher than that of the original Vip3Af (72%)	[67]
Vip3Af	Domain I区域34位点氨基酸M突变为K（M34K）The amino acid M at 34 site in Domain I was mutated to K (M34K)	突变体对棉贪夜蛾（LC₅₀为12.6 ng·cm^-2）的致死毒力较原Vip3Af（LC₅₀为31 ng·cm^-2）提高2.46倍The lethal virulence of the mutant to Spodoptera littoralis (LC₅₀was 12.6 ng·cm^-2) was 2.46-fold higher than that of the original Vip3Af (LC₅₀was 31 ng·cm^-2)	[66]
Sip1Aa	153位点氨基酸G和248位点氨基酸H同时突变为C（G153C/H248C）The amino acids G at 153 and H at 248 sites were mutated to C (G153C/H248C)	突变体对白菜叶甲（LC₅₀为0.614 μg·mL^-1）的致死毒力较原Sip1Aa（LC₅₀为1.696 μg·mL^-1）提高2.76倍The lethal virulence of the mutant to Colaphellus bowringi (LC₅₀was 0.614 μg·mL^-1) was 2.76-fold higher than that of the original Sip1Aa (LC₅₀was 1.696 μg·mL^-1)	[41]
Sip1Aa	β9—β10之间Loop区域128位点氨基酸K突变为A（K128A）The amino acid K at 128 site in the Loop region between β9 and β10 was mutated to A (K128A)	突变体对白菜叶甲（LC₅₀为0.18 μg·mL^-1）的致死毒力较原Sip1Aa（LC₅₀为1.683 μg·mL^-1）提高近10倍The lethal virulence of the mutant to C. bowringi (LC₅₀was 0.18 μg·mL^-1) was nearly 10-fold higher than that of the original Sip1Aa (LC₅₀was 1.683 μg·mL^-1)	[71]

表2

表3

基于Bt毒素的结构域杂合体理性设计实例"

供试模板 Tested template	杂合策略 Heterozygous strategy	实施效果 Implementation effect	参考文献 Reference
Cry9Aa: Cry1Ac	Cry9Aa Domain I替换为Cry1Ac的Domain I Domain I of Cry9Aa was replaced by the Domain I of Cry1Ac	杂合体对棉铃虫（LC₅₀为0.725 ng·cm^-2）的致死毒力较Cry1Ac（LC₅₀为3.564 ng·cm^-2）提高4.9倍，Cry9Aa无杀虫活性The lethal virulence of the hybrid to H. armigera (LC₅₀was 0.725 ng·cm^-2) was 4.9-fold higher than that of the Cry1Ac (LC₅₀was 3.564 ng·cm^-2), and the Cry9Aa had no insecticidal activity	[80]
Cry1Ab: Cry1C	Cry1Ab Domain III替换为Cry1C的Domain III Domain III of Cry1Ab was replaced by the Domain III of Cry1C	杂合体对小菜蛾（LC₅₀为6 ng·cm^-2）的致死毒力较Cry1Ab（LC₅₀为15 ng·cm^-2）和Cry1C（LC₅₀为117 ng·cm^-2）分别提高2.5和19.5倍The lethal virulence of the hybrid to P. xylostella (LC₅₀was 6 ng·cm^-2) was 2.5- and 19.5-fold higher than that of the Cry1Ab (LC₅₀was 15 ng·cm^-2) and Cry1C (LC₅₀was 117 ng·cm^-2), respectively	[94]
Cry1Ab: Cry1Gc	Cry1Ab Domain III替换为Cry1Gc的Domain III Domain III of Cry1Ab was replaced by the Domain III of Cry1Gc	杂合体转基因作物对二化螟和亚洲玉米螟的抗性水平显著增强（原文未显示数值）The resistance level of the hybrid transgenic crops to Chilo suppressalis and O. furnacalis was significantly enhanced (detailed data not shown in article)	[82]
Cry1Ac: Cry1F	Cry1Ac Domain III替换为Cry1F的Domain III Domain III of Cry1Ac was replaced by the Domain III of Cry1F	杂合体对棉铃虫的致死毒力显著提升（原文未显示数值）The lethal virulence of the hybrid to H. armigera was significantly enhanced (detailed data not shown in article)	[95]
Cry3Aa: Cry1Ab	Cry3Aa Domain III替换为Cry1Ab的Domain III Domain III of Cry3Aa was replaced by the Domain III of Cry1Ab	杂合体对玉米根虫的致死毒力显著提升（原文未显示数值）The lethal virulence of the hybrid to D. virgifera was significantly enhanced (detailed data not shown in article)	[96]
Cry1Jb: Cry1Ab	Cry1Jb Domain III替换为Cry1Ab的Domain III Domain III of Cry1Jb was replaced by the Domain III of Cry1Ab	杂合体对棉铃虫（LC₅₀为767.62 ng·mL^-1）的致死毒力较Cry1Jb（LC₅₀为6039.55 ng·mL^-1）提高7.8倍The lethal virulence of the hybrid to H. armigera (LC₅₀was 767.62 ng·mL^-1) was 7.8-fold higher than that of the Cry1Jb (LC₅₀was 6039.55 ng·mL^-1)	[97]
Cry1Ac: Cry2Ac	Cry1Ac Domain III替换为Cry2Ac7的Domain III Domain III of Cry1Ac was replaced by the Domain III of Cry2Ac7	杂合体对大豆夜蛾（LC₅₀为10.20 ng·cm^-2）的致死毒力较Cry1Ac（LC₅₀为20.31 ng·cm^-2）和Cry2Ac（LC₅₀为46.53 ng·cm^-2）分别提高2和4.6倍The lethal virulence of the hybrid to Anticarsia gemmatalis (LC₅₀was 10.20 ng·cm^-2) was 2- and 4.6-fold higher than that of the Cry1Ac (LC₅₀was 20.31 ng·cm^-2) and Cry2Ac (LC₅₀was 46.53 ng·cm^-2), respectively	[98]
Cry1Ac: Cry1Ca	Cry1Ac Domain III替换为Cry1Ca的Domain III Domain III of Cry1Ac was replaced by the Domain III Cry1Ca	杂合体对草地贪夜蛾（LD₅₀为288 ng·cm^-2）的致死毒力较Cry1Ac（LD₅₀>3000 ng·cm^-2）和Cry1Ca（LD₅₀>3000 ng·cm^-2）均提高超过10倍The lethal virulence of the hybrid to S. frugiperda (LD₅₀was 288 ng·cm^-2) was above 10-fold higher than that of the Cry1Ac (LD₅₀>3000 ng·cm^-2) and Cry1Ca (LD₅₀>3000 ng·cm^-2)	[83]
Cry1Ba: Cry1Ac	Cry1Ba Domain III替换为Cry1Ac的Domain III Domain III of Cry1Ba was replaced by the Domain III of Cry1Ac	杂合体对棉铃虫（LC₅₀为319 ng·cm^-2）的致死毒力较Cry1Ba（LC₅₀>6400 ng·cm^-2）提高超过20倍The lethal virulence of the hybrid to H. armigera (LC₅₀为319 ng·cm^-2) was above 20-fold higher than that of the Cry1Ba (LC₅₀>6400 ng·cm^-2)	[85]
Cry1Ca: Cry1Ac	Cry1Ca Domain III替换为Cry1Ac的Domain III Domain III of Cry1Ca was replaced by the Domain III of Cry1Ac	杂合体对棉铃虫（LC₅₀为93 ng·cm^-2）的致死毒力较Cry1Ca（LC₅₀>16000 ng·cm^-2）提高超过172倍The lethal virulence of the hybrid to H. armigera (LC₅₀was 93 ng·cm^-2) was above 172-fold higher than that of the Cry1Ca (LC₅₀>16000 ng·cm^-2)	[85]
Cry1Ba: Cry1Ca	Cry1Ba Domain III替换为Cry1Ca的Domain III Domain III of Cry1Ba was replaced by the Domain III of Cry1Ca	杂合体对烟草天蛾（LC₅₀为85 ng·cm^-2）的致死毒力较Cry1Ca（LC₅₀为155 ng·cm^-2）和Cry1Ba (LC₅₀>1000 ng·cm^-2）分别提高1.82倍和超过11倍The lethal virulence of the hybrid to M. sexta (LC₅₀was 85 ng·cm^-2) was 1.82-fold and above 11-fold higher than that of the Cry1Ca (LC₅₀was 155 ng·cm^-2) and Cry1Ba (LC₅₀>1000 ng·cm^-2), respectively	[84]
Cry1Ea: Cry1Ca	Cry1Ea Domain III（530—587）替换为Cry1Ca的Domain III（533—602）Domain III (530-587) of Cry1Ea was replaced by the Domain III (533-602) of Cry1Ca	杂合体对斜纹夜蛾（EC₅₀为5.8 μg·mL^-1）的致死毒力较Cry1Ca（EC₅₀为23.9 μg·mL^-1）和Cry1Ea（EC₅₀>108 μg·mL^-1）分别提高4.12倍和超过18.62倍The lethal virulence of the hybrid to S. litura (EC₅₀was 5.8 μg·mL^-1) was 4.12-fold and above 18.62-fold higher than that of the Cry1Ca (EC₅₀was 23.9 μg·mL^-1) and Cry1Ea (EC₅₀>108 μg·mL^-1), respectively	[99]
Cry1Gb: Cry1Ig	Cry1Gb Domain III替换为Cry1Ig的Domain III Domain III of Cry1Gb was replaced by the Domain III of Cry1Ig	杂合体（EC₅₀为54.6 ng·cm^-2）对Cry1Fa、Vip3Aa和Cry1A.105/Cry2Ab（EC₅₀>3000 ng·cm^-2）耐药性草地贪夜蛾具有显著致死毒力The hybrid showed significant lethal virulence (EC₅₀was 54.6 ng·cm^-2) to S. frugiperda（EC₅₀>3000 ng·cm^-2), which was resistant to Cry1Fa, Vip3Aa and Cry1A.105/Cry2Ab	[100]
Cry1Ia: Cry1Ba	Cry1Ia Domain III替换为Cry1Ba的Domain III Domain III of Cry1Ia was replaced by the Domain III of Cry1Ba	杂合体对马铃薯甲虫（LC₅₀为22.4 μg·mL^-1）的致死毒力较Cry1Ia（LC₅₀为33.7 μg·mL^-1）和Cry1Ba（LC₅₀为142 μg·mL^-1）分别提高1.5和6.3倍The lethal virulence of the hybrid to L. decemlineata (LC₅₀was 22.4 μg·mL^-1) was 1.5- and 6.3-fold higher than that of the Cry1Ia (LC₅₀was 33.7 μg·mL^-1) and Cry1Ba (LC₅₀was 142 μg·mL^-1), respectively	[101]
Cry1Aa: Cry1Ab: Cry1Ac	Cry1Aa Domain I拼接Cry1Ab Domain II拼接Cry1Ac Domain III Cry1Aa Domain I spliced with Cry1Ab Domain II and Cry1Ac Domain III	杂合体对靶标害虫的防控效果显著高于3种母体毒素（原文未显示数值）The control effect of the hybrid to target pests was significantly higher than that of the three original toxins (detailed data not shown in article)	[102]
Cry1Ac: Cry1Ah: Cry1Ca	Cry1Ac前体肽拼接Cry1Ah Domain I 拼接Cry1Ac Domain II拼接Cry1Ca Domain III Cry1Ac pro-toxin peptide spliced with Cry1Ah Domain I, Cry1Ac Domain II and Cry1Ca Domain III	杂合体杀虫谱更广，特别是显著增强了对部分豆类作物鳞翅目害虫的致死毒力（数据多未细列）The hybrid had a wider insecticidal spectrum, especially significantly enhanced the lethal virulence to some lepidoptera pests of legume crops (detailed data not shown)	[13]
Cry1Ab: Cry1Be: Cry1Ka	Cry1Ab前体肽拼接Cry1Be Domain I Domain II and Cry1Ka Domain III		[13]
Cry1Ab: Cry1Ac: Cry1F	Cry1Ab Domain I拼接Cry1Ac Domain II拼接Cry1F Domain III拼接Cry1Ab C端晶体稳定肽（Domain 4—7）Cry1Ab Domain I spliced with Cry1Ac Domain II, Cry1F Domain III and Cry1Ab C-terminal crystal stable peptide (Domain 4-7)	杂合体对欧洲玉米螟（LC₅₀为0.6 ng·cm^-2）的致死毒力较Cry1Ab（LC₅₀为6 ng·cm^-2）、Cry1Ac (LC₅₀为7 ng·cm^-2）和Cry1Fa（LC₅₀为5 ng·cm^-2)分别提高10、11.6和8.3倍The lethal virulence of the hybrid to Ostrinia nubilalis (LC₅₀was 0.6 ng·cm^-2) was 10-, 11.6- and 8.3-fold higher than that of the Cry1Ab (LC₅₀was 6 ng·cm^-2), Cry1Ac (LC₅₀was 7 ng·cm^-2) and Cry1Fa (LC₅₀was 5 ng·cm^-2), respectively	[87]
Cry1Be: Cry1Ca: Cry1Ab	Cry1Be Domain I—II拼接Cry1Ca Domain III拼接Cry1Ab的C端晶体稳定肽（Domain 4—7）Cry1Be Domain I-II spliced with Cry1Ca Domain III and Cry1Ab C-terminal crystal stable peptide (Domain 4-7)	杂合体对草地贪夜蛾的致死毒力显著增强，特别对Cry1F/Vip3A抗性品系致死效果更为明显The lethal virulence of the hybrid to S. frugiperda was significantly enhanced, in particular, the lethal effect to Cry1F/Vip3A resistant strain S. frugiperda was more obvious	[15]
CryAb: Vip3Aa	Cry1Ab的N端（650个氨基酸）与Vip3Aa的C端（790个氨基酸）融合形成复合物The N-terminal of Cry1Ab (650 aa) fused with the C-terminal of Vip3Aa (790 aa) to form a complex	杂合体转基因水稻对二化螟和稻纵卷叶螟的防治效果显著提升（原文未显示数值）The control effect of the hybrid transgenic rice to C. suppressalis and Cnaphalocrocis medinalis was significantly improved (detailed data not shown in article)	[103]
Cry4Ba: Cry1Ac	Cry4Ba的N端与Cry1Ac的C端融合形成复合物The N-terminal of Cry4Ba fused with the C-terminal of Cry1Ac to form a complex	杂合体对尖音库蚊（LC₁₀₀为2.0 μg·mL^-1）的致死毒力较Cry4Ba（LC₁₀₀>200 μg·mL^-1）提高超过100倍。Cry1Ac未见杀虫活性The lethal virulence of the hybrid to C. pipiens (LC₁₀₀was 2.0 μg·mL^-1) was above 100-fold higher than that of the Cry4Ba (LC₁₀₀>200 μg·mL^-1), and the Cry1Ac had no insecticidal activity	[89]
Vip3Ca: Vip3Aa	Vip3Ca的N端188个氨基酸等量替换为Vip3Aa的N端氨基酸The 188 N-terminal amino acids of Vip3Ca were replaced by the equivalent N-terminal amino acids of Vip3Aa	杂合体对草地贪夜蛾（LC₅₀为133.1 ng·cm^-2）的致死毒力较Vip3Aa （LC₅₀为162.0 ng·cm^-2）和Vip3Ca（LC₅₀>7000 ng·cm^-2）分别提高1.22倍和超过52.63倍The lethal virulence of the hybrid to S. frugiperda (LC₅₀was 133.1 ng·cm^-2) was 1.22-fold and above 52.63-fold higher than that of the Vip3Aa (LC₅₀was 162.0 ng·cm^-2) and Vip3Ca (LC₅₀>7000 ng·cm^-2), respectively	[104]
Vip3Aa: Cry1Ac	Vip3Aa16 C端拼接Cry1Ac的N端片段（⁴⁸----⁶⁰⁹）The C-terminal of Vip3Aa16 was spliced with the N-terminal fragment (⁴⁸----⁶⁰⁹) of Cry1Ac	杂合体对地中海粉螟的致死率较Vip3Aa提高20%（原文未显示数值）The lethality rate of the hybrid to Ephestia kuehniella was 20% higher than that of Vip3Aa (detailed data not shown in article)	[91]
Cry2Aa: Cry2Ad	Cry2Aa N端（1—157 bp）与Cry2Ad C端（1743—1899 bp）同源重组杂合体（R27/30）The homologous recombinant of Cry2Aa N-terminal (1-157 bp) and Cry2Ad C-terminal (1743-1899 bp) to form a hybrid (R27/30)	杂合体（R27/30）对亚洲玉米螟（50 ng·mL^-1死亡率为38.33%）的致死毒力较Cry2Aa（50 ng·mL^-1死亡率为33.33%）提高近15%。Cry2Ad未见杀虫活性The lethal virulence of the hybrid to O. furnacalis (50 ng·mL^-1 with a mortality rate of 38.33%) was 15% higher than that of the Cry2Aa (50 ng·mL^-1 with a mortality rate of 33.33%). Cry2Ad had no insecticidal activity	[105]
Cry2Aa: Photorhabdus luminescens PirB toxin	Cry2A的Domain I替换为PirB toxin基因Domain I of Cry2A was replaced by the gene of PirB toxin	杂合体对甜菜夜蛾（IC₅₀为0.74 μg·mL^-1）的致死毒力较Cry2Aa（IC₅₀为1.78 μg·mL^-1）提高2.41倍The lethal virulence of the hybrid to S. exigua (IC₅₀was 0.74 μg·mL^-1) was 2.41-fold higher than that of the Cry2Aa (IC₅₀was 1.78 μg·mL^-1)	[81]
Cry1Ac: Allium sativum lectin	Cry1Ac Domain III替换为A. sativum lectin基因Domain III of Cry1Ac was replaced by the gene of A. sativum lectin	杂合体对棉红铃虫（LC₁₀₀为0.025 μg·g^-1）和棉铃虫（LC₁₀₀为0.5 μg·g^-1）的致死毒力分别较Cry1Ac（LC₁₀₀分别为0.2和15 μg·g^-1）提高8和30倍The lethal virulence of the hybrid to P. gossypiella (LC₁₀₀was 0.025 μg·g^-1) and H. armigera (LC₁₀₀ was 0.5 μg·g^-1) was 8- and 30-fold higher than that of the Cry1Ac (LC₁₀₀was 0.2 and 15 μg·g^-1), respectively	[86]
Cry1Ac: Ricin B-chain lectin	Cry1Ac的N端与Ricin B-chain lectin基因融合形成杂合体The N-terminal of Cry1Ac fused with the gene of Ricin B-chain lectin to form a complex	杂合体对二化螟（致死率90%）的致死毒力较Cry1Ac（致死率30%）提高3倍；杂合体（致死率>90%）对Cry1Ac耐药性棉贪夜蛾的致死毒力较Cry1Ac（致死率<20%）提高超过4.5倍The lethal virulence of the hybrid to C. suppressalis (with a lethality rate of 90%) was 3-fold higher than that of the Cry1Ac (with a lethality rate of 30%), and to Cry1Ac-resistant S. littoralis (with a lethality rate of >90%) was above 4.5-fold higher than that of the Cry1Ac (with a lethality rate of <20%)	[90]
Cry3Aa: Anoplophora glabripennis midgut Cx-cellulase binding peptide (PCx)	Cry3Aa的N端与PCx基因融合形成杂合体The N-terminal of Cry3Aa fused with the gene of PCx to form a complex	杂合体对光肩星天牛的致死率（>33%）较Cry3Aa（<13%）提高超过2.5倍。PCx未见杀虫活性The lethality rate of hybrid to A. glabripennis (>33%) was above 2.5-fold higher than that of the Cry3Aa (<13%), and the PCx had no insecticidal activity	[92]
Cry1B: maize proteinase inhibitor (MPI) potato carboxypeptidase inhibitor (PCI)	MPI拼接Cry1B前体蛋白拼接PCI形成杂合体（MPI-C-PCI） MPI spliced with Cry1B precursor protein and PCI to form a hybrid	杂合体转基因水稻对二化螟的防控效果显著增强，供试虫体体重较对照减少39.6%—64.6% The control effect of hybrid transgenic rice to C. suppressalis was significantly enhanced, and the body weight of the tested insects was reduced by 39.6%-64.6% compared with that of the control	[93]

表3

表4

基于Bt毒素的抗虫增效应用创新策略"

供试毒素 Tested toxin	增效物 Synergist		实施效果 Implementation effect	参考文献 Reference
Cry1Ab/ Cry1Ac	活化增效物Activating synergist	M. sexta cadherin repeats (CR)^(-)	对烟草天蛾的致死率（>85%）较Cry1Ab（<10%）、Cry1Ac（<15%）单独使用提高8.50、5.66倍以上Its lethality rate to M. sexta (>85%) was above 8.50-, 5.66-fold higher than that of the Cry1Ab (<10%), Cry1Ac (<15%) used alone	[111]
Cry1Ac/ Cry1Ca		S. exigua cadherin-like protein (rSeCad1bp)^(-)	对甜菜夜蛾和棉铃虫的生长发育均显著抑制（体重减少25%—52%）The growth and development of S. exigua and H. armigera (body weight loss of 25%-52%) were significantly inhibited	[112]
Cry1Ac		H. armigera cadherin fragment (HaCad1)^(-)	对棉铃虫的致死率（>80%）较Cry 1Ac（<15%）单独使用提高5.3倍以上Its lethality rate to H. armigera (>80%) was above 5.3-fold higher than that of the Cry1Ac (<15%) used alone	[16]
Cry1B/ Cry1C		S. exigua cadherin-like protein (CR11-MPED)^(-)	对甜菜夜蛾的致死率（38.87%）较Cry1B（24.43%）、Cry1C（15.57%）单独使用提高1.59、2.50倍Its lethality rate to S. exigua (38.87%) was 1.59-, 2.50-fold higher than that of the Cry1B (24.43%), Cry1C (15.57%) used alone	[17]
Cry1Fa		M. sexta cadherin (MsCad), S. frugiperda cadherin (SfCad)^(-)	对草地贪夜蛾的致死毒力分别提高1.8倍（MsCad）和5.2倍（SfCad）Its lethal virulence to S. frugiperda was improved by 1.8-fold (MsCad) and 5.2-fold (SfCad), respectively	[148]
Cry3Aa/ Cry3Bb		D. virgifera cadherin repeats (CR)^(-)	对马铃薯甲虫、黄瓜甲虫和玉米根虫的致死毒力提高3—13倍（数据多未细列）Its lethal virulence to L. decemlineata, Diabrotica undecimpunctata and D. virgifera was improved by 3-13 folds (detailed data not shown)	[149]
Cry1Ac		M. sexta aminopeptidase^(-), phosphatase^(-)	对烟草天蛾幼虫肠壁细胞损害程度显著增强（原文未显示数值）Its damage degree to the intestinal wall cells of M. sexta larvae was significantly enhanced (detailed data not shown in article)	[150]
Cry8Hb/ Cry3-type		Escherichia coli maltose binding protein (MBP)^(-)	对玉米根虫（EC₅₀为16.1 ng·mL^-1）的致死毒力较Cry8Hb/Cry3-type（EC₅₀为214 ng·mL^-1）单独使用提高13.3倍Its lethal virulence to D. virgifera (EC₅₀ was 16.1 ng·mL^-1) was 13.3-fold higher than that of the Cry8Hb/Cry3-type (EC₅₀ was 214 ng·mL^-1) used alone	[113]
Cry2Aa	靶向受体结合增效物Targeted receptor binding synergist	B. thuringiensis P20 helper protein^(-)	对地中海粉螟、尖音库蚊和埃及伊蚊的致死毒力较对照组Cry2Aa分别提高1.43、341.28和354.62倍（数据多未细列）Its lethal virulence to Ephestia kuehniella, C. pipiens and A. aegypti was 1.43-, 341.28- and 354.62-fold higher than that of the Cry2Aa control (detailed data not shown)	[19]
Cry1Ab/ Cry1Ac		P. xylostella Hsp90 (PxHsp90) chaperone protein^(-)	对小菜蛾和草地贪夜蛾的致死率提高4—8倍（数据多未细列）Its lethality rate to P. xylostella and S. frugiperda was improved by 4-8 folds (detailed data not shown)	[18]
Cry1Ac		Bacillus enhancin-like protein (Bel)^(-)	对棉铃虫致死率（74.4%）较Cry1Ac（34.2%）单独使用提高2.18倍Its lethality rate to H. armigera (74.4%) was 2.18-fold higher than that of the Cry1Ac (34.2%) used alone	[114]
Cry2Aa	表达增效物Expression synergist	B. thuringiensis P20 helper protein^(-)	促进Cry2Aa在苏云金芽孢杆菌中的表达量提高7倍The protein expression of Cry2Aa in B. thuringiensis increased by 7-fold	[19]
Cry10A/ Cyt1C		B. thuringiensis QBT220-pBtoxis plasmid^(-)	Cry10A/Cyt1C蛋白表达量提高1.29倍，对埃及伊蚊的致死毒力同步增强1.5倍The protein expression of Cry10A/Cyt1C increased by 1.29-fold, and the lethal virulence to A. aegypti increased by 1.5-fold	[115]
Vip3Aa		B. thuringiensis strong promoter (P_rsi)^(-)+ Protease gene knocked out B. thuringiensis strains (BMB171)^(-)	Vip3Aa蛋白表达量显著提高，且对甜菜夜蛾（LC₅₀为13.05 μL·g^-1）的致死毒力较对照（LC₅₀为59.72 μL·g^-1）提高4.58倍The protein expression of Vip3Aa increased significantly, and the lethal virulence to S. exigua (LC₅₀ was 13.05 μL·g^-1) was 4.58-fold than that of the control (LC₅₀ was 59.72 μL·g^-1)	[116]
Cry1Ac		Cotton leaf curl Kokhran virus-Burewala strong promoter (CLCuKoV-Bu)^(-)	转基因棉中Cry1Ac蛋白表达量提升3倍，间接增强转基因作物对靶标害虫的防控能力The protein expression of Cry1Ac in transgenic cotton increased by 3-fold, which indirectly enhanced the ability of transgenic crops to control target pests	[117]
Cry1Ah		Maize ubi1 intron^(-)	转基因玉米中Cry1Ah蛋白表达量提高20%，间接增强转基因作物对靶标害虫的防控能力The protein expression of Cry1Ah in transgenic maize increased by 20%, which indirectly enhanced the ability of transgenic crops to control target pests	[118]
Cry1Ab/ Cry1Ac		Azotobacter^(-)	促进Cry1Ab/Cry1Ac蛋白表达，对棉铃虫的防控效果显著提高（原文未显示数值）It promoted the protein expression of Cry1Ab/Cry1Ac, and the control effect to H. armigera was significantly improved (detailed data not shown in article)	[119]
Cry1Ac		Amino acids^(-)	转基因棉中Cry1Ac蛋白表达量提高15.2%—25.8%，间接增强转基因作物对靶标害虫的防控能力The protein expression of Cry1Ac in transgenic cotton increased by 15.2%-25.8%, which indirectly enhanced the ability of transgenic crops to control target pests	[120]
Cry11Aa		Late embryogenesis abundant peptide (LEA-II)^(-)	促进Cry11Aa蛋白表达量提升3倍，间接增强表达制剂对靶标害虫的防控能力The protein expression of Cry11Aa increased by 3-fold, which indirectly enhanced the ability of expression products to control target pests	[20]
Cry1C	同源协同增效物Homology cooperative synergist	Cry1Aa⁽⁺⁾	对甜菜夜蛾（LC₅₀为0.537 mg·g^-1）的致死毒力较Cry1C（LC₅₀为1.466 mg·g^-1）和Cry1Aa（LC₅₀为3.936 mg·g^-1）单独使用提高2.73和7.33倍Its lethal virulence to S. exigua (LC₅₀为0.537 mg·g^-1) was 2.73- and 73.3-fold higher than that of the Cry1C (LC₅₀ was 1.466 mg·g^-1) and Cry1Aa (LC₅₀was 3.936 mg·g^-1) used alone	[151]
Cry3A		Bt spores⁽⁺⁾	对马铃薯甲虫的致死毒力较两者单独使用提高2.6倍（Cry3A）和4.9倍（Bt spores）Its lethal virulence to L. decemlineata was 2.6- and 4.9-fold higher than that of the Cry3A and Bt spores used alone	[152]
Cry4Aa		Cyt2Ba⁽⁺⁾	对埃及伊蚊（LC₅₀为13.41 ng·mL^-1）的致死毒力较Cry4Aa（LC₅₀为34.63 ng·mL^-1）和Cyt2Ba（LC₅₀为279.37 ng·mL^-1）单独使用提高2.58和20.83倍Its lethal virulence to A. aegypti (LC₅₀ was 13.41 ng·mL^-1) was 2.58- and 20.83-fold higher than that of the Cry4Aa (LC₅₀ was 34.63 ng·mL^-1) and Cyt2Ba (LC₅₀ was 279.37 ng·mL^-1) used alone	[128]
Cry4Ba		Cyt2Aa⁽⁺⁾	对埃及伊蚊（LC₅₀为7 ng·mL^-1）和致倦库蚊（LC₅₀为20 ng·mL^-1）的致死毒力较Cry4Ba （LC₅₀分别为140 ng·mL^-1和无活性）和Cyt2Aa（LC₅₀分别为350和250 ng·mL^-1）单独使用提高12.5—50倍Its lethal virulence to A. aegypti (LC₅₀ was 7 ng·mL^-1) and C. quinquefasciatus (LC₅₀ was 20 ng·mL^-1) was 12.5-50 folds higher than that of the Cry4Ba (LC₅₀ was 140 ng·mL^-1 and inactive) and Cyt2Aa (LC₅₀ was 350 and 250 ng·mL^-1) used alone	[21]
Cry9Aa		Vip3Aa⁽⁺⁾	对二化螟（LC₅₀为0.13 μg·g^-1）的致死毒力较Cry9Aa（LC₅₀为0.70 μg·g^-1）和Vip3Aa（LC₅₀为37.41 μg·g^-1）单独使用提高5.38和287.76倍Its lethal virulence to C. suppressalis (LC₅₀ was 0.13 μg·g^-1) was 5.38- and 287.76-fold higher than that of the Cry9Aa (LC₅₀ was 0.70 μg·g^-1) and Vip3Aa (LC₅₀ was 37.41 μg·g^-1) used alone	[131]
Cry9Ee		Vip3Aa⁽⁺⁾	对二化螟（LC₅₀为1.78 μg·g^-1）的致死毒力较Cry9Ee（LC₅₀为1.96 μg·g^-1）和Vip3Aa（LC₅₀为27.77 μg·g^-1）单独使用提高1.1和15.6倍Its lethal virulence to C. suppressalis (LC₅₀ was 1.78 μg·g^-1) was 1.1- and 15.6-fold higher than that of the Cry9Ee (LC₅₀ was 1.96 μg·g^-1) and Vip3Aa (LC₅₀ was 27.77 μg·g^-1) used alone	[132]
Cry10Aa		Cyt2Ba⁽⁺⁾	对埃及伊蚊（LC₅₀为4.22 ng·mL^-1）的致死毒力较Cry10Aa（LC₅₀为299.62 ng·mL^-1）和Cyt2Ba（LC₅₀为279.37 ng·mL^-1）单独使用提高71和66.2倍Its lethal virulence to A. aegypti (LC₅₀ was 4.22 ng·mL^-1) was 71- and 66.2-fold higher than that of the Cry10Aa (LC₅₀ was 299.62 ng·mL^-1) and Cyt2Ba (LC₅₀ was 279.37 ng·mL^-1) used alone	[128]
Cry11Aa		Cyt1Aa⁽⁺⁾	对白纹伊蚊（LC₅₀为17.1 ng·mL^-1）的致死毒力较Cry11Aa（LC₅₀为228 ng·mL^-1）和Cyt1Aa（LC₅₀为171 ng·mL^-1）单独使用提高13.3和10倍Its lethal virulence to A. albopictus (LC₅₀ was 17.1 ng·mL^-1) was 13.3- and 10-fold higher than that of the Cry11Aa (LC₅₀ was 228 ng·mL^-1) and Cyt1Aa (LC₅₀ was 171 ng·mL^-1) used alone	[129]
Cry11Ba		Cry4Aa⁽⁺⁾	对尖音库蚊（LC₅₀为0.04 μg·mL^-1）的致死毒力较Cry11Ba（LC₅₀为0.11 μg·mL^-1）和Cry4Aa（LC₅₀为0.97 μg·mL^-1）单独使用提高2.75和24.25倍Its lethal virulence to C. pipiens (LC₅₀ was 0.04 μg·mL^-1) was 2.75- and 24.25-fold higher than that of the Cry11Ba (LC₅₀ was 0.11 μg·mL^-1) and Cry4Aa (LC₅₀ was 0.97 μg·mL^-1) used alone	[130]
Cry21Fa		Cry21Ha⁽⁺⁾	对秀丽隐杆线虫（LC₅₀为6.1 μg·mL^-1）的致死毒力较Cry21Fa（LC₅₀为13.6 μg·mL^-1）和Cry21Ha（LC₅₀为23.9 μg·mL^-1）单独使用提高2.23和3.92倍Its lethal virulence to C. elegans (LC₅₀为6.1 μg·mL^-1) was 2.23- and 3.92-fold higher than that of the Cry21Fa (LC₅₀ was 13.6 μg·mL^-1) and Cry21Ha (LC₅₀ was 23.9 μg·mL^-1) used alone	[153]
Cry64Ba		Cry64Ca⁽⁺⁾	对灰飞虱（LC₅₀为3.15 μg·mL^-1）和白背飞虱（LC₅₀为2.14 μg·mL^-1）的致死毒力显著增强（原文未显示可比对数值）Its lethal virulence to Laodelphax striatellus (LC₅₀ was 3.15 μg·mL^-1) and Sogatella furcifera (LC₅₀ was 2.14 μg·mL^-1) was significantly enhanced (detailed comparable data not shown in article)	[33]
Cyt1Aa		Cry1Ca⁽⁺⁾	对埃及伊蚊（LC₅₀为0.61 μg·mL^-1）的致死毒力较Cyt1Aa（LC₅₀为0.73 μg·mL^-1）和Cry1Ca（LC₅₀为4.61 μg·mL^-1）单独使用提高1.2和7.56倍Its lethal virulence to A. aegypti (LC₅₀ was 0.61 μg·mL^-1) was 1.2- and 7.56-fold higher than that of the Cyt1Aa (LC₅₀ was 0.73 μg·mL^-1) and Cry1Ca (LC₅₀ was 4.61 μg·mL^-1) used alone	[127]
Cyt1Aa		Cry2Aa⁽⁺⁾	对致倦库蚊（LC₅₀为15.2 μg·mL^-1）的致死毒力较Cyt1Aa（LC₅₀为31.3 μg·mL^-1）和Cry2Aa（LC₅₀>200 μg·mL^-1）单独使用提高2.05倍和超过13倍Its lethal virulence to C. quinquefasciatus (LC₅₀为15.2 μg·mL^-1) was 2.05-fold and above 13-fold higher than that of the Cyt1Aa (LC₅₀ was 31.3 μg·mL^-1) and Cry2Aa (LC₅₀>200 μg·mL^-1) used alone	[122]
Cyt1Aa		Cry4Ba⁽⁺⁾	对埃及伊蚊（LC₅₀为66.7 ng·mL^-1）的致死毒力较Cyt1Aa（LC₅₀为952.5 ng·mL^-1）和Cry4Ba（LC₅₀为79.4 ng·mL^-1）单独使用提高14.28和1.19倍Its lethal virulence to A. aegypti (LC₅₀ was 66.7 ng·mL^-1) was 14.28- and 1.19-fold higher than that of the Cyt1Aa (LC₅₀ was 952.5 ng·mL^-1) and Cry4Ba (LC₅₀ was 79.4 ng·mL^-1) used alone	[63]
Vip3Aa		Cry1F⁽⁺⁾	对东方黏虫（LC₅₀为1.8 μg·g^-1）的致死毒力较Vip3Aa（LC₅₀为7.4 μg·g^-1）和Cry1F（LC₅₀为14.4 μg·g^-1）单独使用提高4.1和8倍 Its lethal virulence to Mythimna separata (LC₅₀ was 1.8 μg·g^-1) was 4.1- and 8-fold higher than that of the Vip3Aa (LC₅₀ was 7.4 μg·g^-1) and Cry1F (LC₅₀ was 14.4 μg·g^-1) used alone	[133]
Vip3Aa		Cry1Ie⁽⁺⁾	对东方黏虫（LC₅₀为2.0 μg·g^-1）的致死毒力较Vip3Aa（LC₅₀为7.4 μg·g^-1）和Cry1Ie（LC₅₀为78.6 μg·g^-1）单独使用提高3.7和39.3倍Its lethal virulence to M. separata (LC₅₀ was 2.0 μg·g^-1) was 3.7- and 39.3-fold higher than that of the Vip3Aa (LC₅₀ was 7.4 μg·g^-1) and Cry1Ie (LC₅₀ was 78.6 μg·g^-1) used alone	[133]
Cry11Aa		Cyt1A-like δ endotoxins⁽⁺⁾	对白纹伊蚊（LC₅₀为19.7 ng·mL^-1）的致死毒力较Cry11Aa（LC₅₀为228 ng·mL^-1）和Cyt1A-like（LC₅₀>10⁵ ng·mL^-1）单独使用提高11.5和超过5000倍Its lethal virulence to A. albopictus (LC₅₀ was 19.7 ng·mL^-1) was 11.5-fold and above 5000-fold higher than that of the Cry11Aa (LC₅₀ was 228 ng·mL^-1) and Cyt1A-like (LC₅₀>10⁵ ng·mL^-1) used alone	[129]
Cry11Aa		Cry-like δ endotoxins (Mtx-1)⁽⁺⁾	对致倦库蚊（LC₉₅为1.93 μg·mL^-1）的致死毒力较Cry11Aa（LC₉₅为33.5 μg·mL^-1）和Mtx-1（LC₉₅为2.4 μg·mL^-1）单独使用提高17.36和1.24倍Its lethal virulence to C. quinquefasciatus (LC₉₅ was 1.93 μg·mL^-1) was 17.36- and 1.24-fold higher than that of the Cry11Aa (LC₉₅ was 33.5 μg·mL^-1) and Mtx-1 (LC₉₅ was 2.4 μg·mL^-1) used alone	[154]
Cyt1Aa		L. sphaericus binary toxin (BinA)⁽⁺⁾	对Bt耐药性致倦库蚊（LC₅₀为10.605 μg·mL^-1）的致死毒力较Cyt1Aa（LC₅₀>50 μg·mL^-1）和BinA（极低活性）单独使用显著提高Its lethal virulence to Bt-resistance C. quinquefasciatus (LC₅₀ was 10.605 μg·mL^-1) was significantly enhanced than that of the Cyt1Aa (LC₅₀>50 μg·mL^-1) and BinA (very low activity) used alone	[134]
Cry5Ba	异源协同增效物Heterology cooperative synergist	B. thuringiensis metalloproteinase (Bmp1)⁽⁺⁾	对秀丽隐杆线虫（LC₅₀为37.5 μg·mL^-1）的致死毒力较Cry5Ba（LC₅₀为226.67 μg·mL^-1）和Bmp1（LC₅₀为610 μg·mL^-1）单独使用提高6.04和16.27倍Its lethal virulence to C. elegans (LC₅₀ was 37.5 μg·mL^-1) was 6.04- and 16.27-fold higher than that of the Cry5Ba (LC₅₀ was 226.67 μg·mL^-1) and Bmp1 (LC₅₀ was 610 μg·mL^-1) used alone	[155]
Cry1Ac		B. thuringiensis chitinase⁽⁺⁾	对甜菜夜蛾（LC₅₀为4.4 μg·mL^-1）和棉铃虫（LC₅₀为5.8 μg·mL^-1）的致死毒力较Cry1Ac（LC₅₀分别为6.8和8.8 μg·mL^-1）单独使用分别提高1.55和1.52倍；chitinase单独使用的致死率分别为11.7%和8.2% Its lethal virulence to S. exigua (LC₅₀ was 4.4 μg·mL^-1) and H. armigera (LC₅₀ was 5.8 μg·mL^-1) was 1.55- and 1.52-fold higher than that of the Cry1Ac (LC₅₀ was 6.8 and 8.8 μg·mL^-1) used alone, and the lethality rate of chitinase used alone was 11.7% and 8.2%, respectively	[22]
Cry1Ac		Nicotiana tabacum chitinase⁽⁺⁾	共表达制剂对棉铃虫（LC₅₀为4.79 μg·mL^-1）的致死毒力较Cry1Ac（LC₅₀为89.86 μg·mL^-1）制剂单独使用提高18.76倍；chitinase单独使用为较低活性Its lethal virulence of coexpression products to H. armigera (LC₅₀ was 4.79 μg·mL^-1) was 18.76-fold higher than that of the Cry1Ac (LC₅₀ was 89.86 μg·mL^-1) used alone, and the chitinase used alone was low activity	[156]
Cry21Aa		Pseudomonas aeruginosa chitinase (pachi)⁽⁺⁾	对秀丽隐杆线虫（LC₅₀为30.9 μg·mL^-1）的致死毒力较Cry21Aa（LC₅₀为78.7 μg·mL^-1）和pachi（LC₅₀为387.3 μg·mL^-1）单独使用分别提高2.55和12.53倍Its lethal virulence to C. elegans (LC₅₀ was 30.9 μg·mL^-1) was 2.55- and 12.53-fold higher than that of the Cry21Aa (LC₅₀ was 78.7 μg·mL^-1) and pachi (LC₅₀ was 387.3 μg·mL^-1) used alone	[157]
Cry1Ac		Cowpea trypsin inhibitor (CpTI)⁽⁺⁾	共表达转基因棉对非靶标害虫棉蚜的防治能力显著增强（原文未显示数值）The ability of coexpression transgenic cotton to control non-target pest Aphis gossypii was significantly enhanced	[158]
Cry4Ba		Enterolobium contortisiliquum trypsin inhibitor (EcTI)⁽⁺⁾	对埃及伊蚊的致死率（~85%）较Cry4Ba（~25%）和EcTI（极低活性）单独使用显著提高Its lethality rate to A. aegypti (~85%) was significantly improved than that of the Cry4Ba (~25%) and EcTI (very low activity) used alone	[23]
Cry3A-SN- 19 hybrid		Oryza proteinase inhibitor cystatin II (OCII)⁽⁺⁾	共表达转基因马铃薯植株对马铃薯甲虫的防控效果显著提高（原文未显示数值）The control effect of coexpression transgenic potato to L. decemlineata was significantly improved (detailed data not shown in article)	[159]
Vip3Aa		A. sativum lectin (ASAL)⁽⁺⁾	共表达转基因棉对棉铃虫和烟粉虱的防控效果显著提高（原文未显示数值）The control effect of coexpression transgenic cotton to H. armigera and Bemisia tabaci was significantly improved (detailed data not shown in article)	[160]
Cry1Ab		A. sativum lectin (ASAL)⁽⁺⁾	共表达转基因水稻对三化螟、二化螟和稻纵卷叶螟的防控效果显著，虫体死亡率提升87%—93% The control effect of coexpression transgenic rice to S. incertulas, C. suppressalis and C. medinalis was significantly improved, the mortality rate of pests was increased by 87%-93%	[24]
Cry1Ac		Galanthus nivalis lectin (GNA)⁽⁺⁾	共表达转基因棉对棉贪夜蛾和棉蚜的致死率提高46.6%—66.2% The lethality rate of coexpression transgenic cotton to S. littoralis and A. gossypii was increased by 46.6%-66.2%	[161]
Cry1Ac		Chloroplast transit peptide (TP)^(-)+ Ricin B-chain (RB)⁽⁺⁾	共表达转基因棉中融合蛋白表达量提高近6倍，且对棉铃虫和棉红铃虫的致死率均提高超过30% The fusion protein expression in coexpression transgenic cotton was improved by nearly 6-fold, and the mortality rate of H. armigera and Pictinophora scutigera was increased by more than 30%	[162]
Cry1Ac		Selenocosmia huwena venom neurotoxin (hwtx-I)⁽⁺⁾	共表达制剂对小菜蛾（LC₅₀为5.12 μg·mL^-1）的致死毒力较Cry1Ac（LC₅₀为70.78 μg·mL^-1）单独使用提高13.8倍；hwtx-I单独使用活性较低The lethal virulence of coexpression products to P. xylostella (LC₅₀ was 5.12 μg·mL^-1) was 13.8-fold higher than that of Cry1Ac (LC₅₀ was 70.78 μg·mL^-1) used alone, and hwtx-I was low activity when used alone	[163]
Cry1Ac		Australian funnel-web spider venom neurotoxin (ω-ACTX -Hv1a)⁽⁺⁾	对甜菜夜蛾（LC₅₀为83.19 μg·mL^-1）的致死毒力较Cry1Ac（LC₅₀>500 μg·mL^-1）和ω-ACTX-Hv1a（较低活性）单独使用显著增强The lethal virulence to S. exigua (LC₅₀ was 83.19 μg·mL^-1) was significantly enhanced than that of Cry1Ac (LC₅₀>500 μg·mL^-1) and ω-ACTX-Hv1a (lower activity) used alone	[164]
Cry1Ac		Hadronyche versuta venom neurotoxin (hv1a+hv2a)⁽⁺⁾	对棉铃虫的致死毒力较Cry1Ac、hv1a和hv2a单独使用分别提高1.32、1.26和1.14倍The lethal virulence to H. armigera was 1.32-, 1.26- and 1.14-fold higher than that of Cry1Ac, hv1a and hv2a used alone	[165]
Cry1Ac		Anemonia viridis neurotoxin (Av3)⁽⁺⁾	对棉铃虫（LC₅₀为11.9 μg·mL^-1）的致死毒力较Cry1Ac（LC₅₀为30.7 μg·mL^-1）和Av3 Cry1Ac（LC₅₀>10⁴ μg·mL^-1）单独使用提高2.6倍和超过840倍The lethal virulence to H. armigera (LC₅₀为11.9 μg·mL^-1) was 2.6-fold and above 840-fold higher than that of Cry1Ac (LC₅₀ was 30.7 μg·mL^-1) and Av3 Cry1Ac (LC₅₀>10⁴ μg·mL^-1) used alone	[166]
Cry2Ab		Avermectin⁽⁺⁾	对小菜蛾（IC₅₀为0.01 μg·cm^-2）的致死毒力较Cry2Ab（IC₅₀为1.544 μg·cm^-2）和阿维菌素（IC₅₀为~1 μg·cm^-2）单独使用提高154.4和~100倍The lethal virulence to P. xylostella (IC₅₀ was 0.01 μg·cm^-2) was 154.4- and ~100-fold higher than that of Cry2Ab (IC₅₀ was 1.544 μg·cm^-2) and avermectin (IC₅₀ was ~1 μg·cm^-2) used alone	[137]
Cry4Ba		Calcofluor⁽⁺⁾	对埃及伊蚊（LC₅₀为0.29 μg·mL^-1）的致死毒力较Cry4Ba（LC₅₀为6.27 μg·mL^-1）和Calcofluor（致死率<10%）单独使用显著增强The lethal virulence to A. aegypti (LC₅₀ was 0.29 μg·mL^-1) was significantly enhanced than that of Cry4Ba (LC₅₀ was 6.27 μg·mL^-1) and Calcofluor (lethality rate<10%) used alone	[167]
Cyt2Ba		White pepper powder (WP)⁽⁺⁾	对白纹伊蚊24 h致死率（80%）较Cyt2Ba（40%）单独使用提高2倍，white pepper powder单独使用活性较低Its lethality rate to A. albopictus (80%) in 24 h was 2-fold higher than that of Cyt2Ba (40%) used alone, and white pepper powder was lower activity when used alone	[168]
Cry1-type		Mustard oil⁽⁺⁾	对欧洲松毛虫致死率（83.4%）较Bt Cry（30%）和mustard oil（6.7%）单独使用分别提高2.78和12.45倍Its lethality rate to Dendrolimus pini (83.4%) was 2.78- and 12.45-fold higher than that of Bt Cry (30%) and mustard oil (6.7%) used alone	[138]
Cry1-type		Carvacrol⁽⁺⁾	对甜菜夜蛾的致死率（96.7%）较Cry1-type（56.7%）和carvacrol（23.4%）单独使用提高1.71和4.13倍Its lethality rate to S. exigua (96.7%) was 1.71- and 4.13-fold higher than that of Cry1-type (56.7%) and carvacrol (23.4%) used alone	[169]
Cry1Ac		Flavone⁽⁺⁾	对棉铃虫的致死率（>90%）较Cry1Ac（<22%，3 ng·cm^-2）和flavone（<40%，0.7 mg·g^-1）单独使用提高超过68%和50% Its lethality rate to H. armigera (>90%) was above 68% and 50% than that of Cry1Ac (<22%, 3 ng·cm^-2) and flavone (<40%, 0.7 mg·g^-1) used alone	[139]
Cyt2Ba		B. bassiana⁽⁺⁾	共表达制剂对埃及伊蚊和白纹伊蚊的致死毒力较Cyt2Ba单独使用分别提高47%和33%，球孢白僵菌单独使用活性较低The lethal virulence of coexpression products to A. aegypti and A. albopictus was improved by 47% and 33% than that of Cyt2Ba used alone, and B. bassiana was lower activity when used alone	[140]
Vip3A		B. bassiana (BbV28)⁽⁺⁾	共表达制剂对斜纹夜蛾的3 d致死毒力较球孢白僵菌单独使用提高26.2倍，原文Vip3A的活性数据未显示The lethal virulence of coexpression products to S. litura in 3 days was 26.2-fold higher than that of B. bassiana used alone, and the detailed data for Vip3A was not shown in article	[170]
Cry3Bb		Plagiodera versicolora gut bacterium (Pseudomonas putida)⁽⁺⁾	对柳蓝叶甲的致死率显著提高（原文未显示数值）Its lethality rate to P. versicolora was significantly improved (detailed data not shown in article)	[171]
Cry4Ba		X. nematophila⁽⁺⁾	对埃及伊蚊（LC₅₀为2.02 ng·mL^-1）的致死毒力较Cry4Ba（LC₅₀为21.28 ng·mL^-1）单独使用提高10.5倍，对埃及伊蚊的致死率（95%）较嗜线虫致病杆菌（52%）单独使用提高43% Its lethal virulence to A. aegypti (LC₅₀ was 2.02 ng·mL^-1) was 10.5-fold higher than that of Cry4Ba (LC₅₀ was 21.28 ng·mL^-1) used alone, and the lethality rate to A. aegypti (95%) was 43% higher than that of X. nematophila (52%) used alone	[141]
Cry4Ba		P. luminescens⁽⁺⁾	对埃及伊蚊（LC₅₀为8.49 ng·mL^-1）的致死毒力较Cry4Ba（LC₅₀为21.28 ng·mL^-1）提高2.5倍，对埃及伊蚊的致死率（87%）较P. luminescens（43%）单独使用提高44% Its lethal virulence to A. aegypti (LC₅₀ was 8.49 ng·mL^-1) was 2.5-fold higher than that of Cry4Ba (LC₅₀ was 21.28 ng·mL^-1) used alone, and the lethality rate to A. aegypti (87%) was 44% higher than that of P. luminescens (43%) used alone	[141]
Cry4Aa		B. mori cypovirus (BmCPV)⁽⁺⁾	对紫外线的耐受稳定性显著增强，且对白纹伊蚊的致死率显著提高Its tolerance stability to UV radiation was significantly enhanced, and the lethality rate to A. albopictus was significantly increased	[172]
Cry1Ab		Autographa californica multiple nuclearpolyhedrosis virus (AcMNPV)⁽⁺⁾	共表达制剂对棉贪夜蛾（LC₅₀为1.7 μg·mL^-1）的致死毒力较AcMNPV（LC₅₀为10 μg·mL^-1）单独使用提高5.88倍，原文Cry1Ab的活性数据未显示The lethal virulence of coexpression products to S. littoralis (LC₅₀ was 1.7 μg·mL^-1) was 5.88-fold higher than that of AcMNPV (LC₅₀ was 10 μg·mL^-1) used alone, and the detailed data for Cry1Ab was not shown in article	[142]
Cry1-5		Araneus ventricosus spider toxin (Av-Tox2)⁽⁺⁾+ AcMNPV⁽⁺⁾	共表达制剂对小菜蛾和甜菜夜蛾的致死率提升超过50%和75% The lethality rate of coexpression products to P. xylostella and S. exigua was increased by more than 50% and 75%	[25]
Cry1-5		Androctonus australis neurotoxin (AaIT)⁽⁺⁾+ AcMNPV⁽⁺⁾	共表达制剂对小菜蛾和甜菜夜蛾的致死毒力提升超过9和1.5倍The lethal virulence of coexpression products to P. xylostella and S. exigua was increased by more than 9- and 1.5-fold	[143]
Cry1-5		Bombus ignites venom Kunitz-type toxin (KTI)⁽⁺⁾+AcMNPV⁽⁺⁾	共表达制剂对小菜蛾和甜菜夜蛾的致死率提升超过75%和80% The lethality rate of coexpression products to P. xylostella and S. exigua was increased by more than 75% and 80%	[173]
Cry1Ab		O. furnacalis chymotrypsins- like genes dsRNA (dsCTPs)⁽⁺⁾	对亚洲玉米螟的致死率（100%）较Cry1Ab（<60%）和dsCTPs（<20%）单独使用提高超过40%和80% Its lethality rate to O. furnacalis (100%) was increased by above 40% and 80% than that of Cry1Ab (<60%) and dsCTPs (<20%) used alone	[144]
Cry1Ca		S. exigua dsRNA specific to integrin β1 subunit (dsINT)⁽⁺⁾	对甜菜夜蛾的致死率（80%）较Cry1Ca（58%）和dsINT（<50%）单独使用提高22%和超过30% Its lethality rate to S. exigua (80%) was increased by 22% and above 30% than that of Cry1Ca (58%) and dsINT (<50%) used alone	[174]

表4

参考文献 180

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主要作用对象The main target	代表性Bt毒素Representative Bt toxin
鳞翅目Lepidoptera	Cry1Aa,b,c,d,e,g,h/1Bd,e/1Ca/1Da,b/1Ea,b/1Fa/1Ga,b/1Ha,b/1Id/1Ja,b/1Ka、Cry2Aa,b,h、Cry7B、Cry8D、Cry9Aa/9Ba/ 9Ca/9Ea、Cry15A、Cry22A、Cry32A、Cry51A；Vip3
鞘翅目Coleoptera	Cry1Ba/Ia、Cry3Aa/Ba,b/Ca、Cry6Aa,b、Cry7Aa,b、Cry8Ab/Ca/Da,b/Ea/Ka/Na、Cry10Aa、Cry22Aa,b、Cry23Aa、Cry34Aa,b,c/Ba、Cry35Aa,b,c/Ba、Cry36Aa、Cry37Aa、Cry51Aa；Cyt1Aa、Cyt2Ca；Vip1Ad/Ca/Da+Vip2Aa,d,g、Vip4；Sip1Aa,b
双翅目Diptera	Cry1A/1B/1C、Cry2A、Cry4Aa/4Ba、Cry10Aa、Cry11Aa/11Ba,b、Cry16A、Cry19Aa/19Ba、Cry20Aa、Cry24C、Cry27A、Cry32B/32C/32D、Cry39A、Cry44A、Cry47A、Cry48A、Cry49A；Cyt1A/1B、Cyt2A/2B
半翅目Hemiptera	Cry2A、Cry3A、Cry11A；Vip1、Vip2
膜翅目Hymenoptera	Cry3A、Cry5A、Cry22A
线虫Rhabditida	Cry5A/5B、Cry6A/6B、Cry12A、Cry13A、Cry14A、Cry21A、Cry55A
蜗牛Fruticicolidae	Cry1Ab
人类癌细胞 Human cancer cell	Cry31Aa,b,c（Parasporin1）、Cry41Aa,b（Parasporin3）、Cry42A、Cry45Aa（Parasporin4）、Cry46Aa,b（Parasporin2）、Cry63A、Cry64Aa/Ba/Ca（Parasporin5）

基于Bt毒素的杀虫蛋白理性设计与创新应用策略

Rational Design and Innovative Application Strategy for the Insecticidal Protein Based on Bt Toxin

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