Genetic Modification Approaches for Parasporins Bacillus thuringiensis Proteins with Anticancer Activity
Abstract
:1. Background
2. Overview of the Classification and Structure of Parasporins Found in Bacillus thuringiensis Strains
β-Type-Like Pore-Forming Parasporins
3. Effects of Parasporins on Cancer Cells
4. Perspectives on the Improvement of Bt Parasporins as an Innovative Strategy for Controlling Cancer Cells
Genetic Improvement of Cry Protein as a Model to Be Followed for Parasporins
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Sample Availability
References
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Parasporin | Strain (Bt) | Molecular Mass (kDa) | Target Cell Line | Cytotoxic Activity IC50 (μg/mL) | Ref. |
---|---|---|---|---|---|
PS1Aa1 | A1190 | 81 | MOLT-4 HL-60 HepG2 HeLa Jurkat Sawano Caco-2 A549 | 2.2 0.32 3.0 0.12 >10 >10 >10 >10 | [9,13,14] |
PS2Aa1 | A1547 | 37 | MOLT-4 Jurkat HL-60 HepG2 Sawano Caco-2 HCT116 CCRF-CEM | 0.022 0.018 0.019 0.019 0.0017 0.013 10 27 | [8,9,14,15] |
PS3Aa1 | A1462 | 93 | MOLT-4 Jurkat HL-60 HepG2 HeLa Sawano | >10 >10 1.32 2.8 >10 >10 | [9,14,16] |
PS4Aa1 | A1470 | 34 | MOLT-4 HL-60 HepG2 Sawano TCS Caco-2 | 0.472 0.725 1.90 0.245 0.719 0.124 | [9,14,17] |
PS5Aa1 | A1100 | 31 | MOLT-4 Caco-2 HepG2 TCS HeLa Sawano. | 0.075 0.30 0.049 0.046 0.08 0.065 | [14,18] |
PS6Aa1 | M109/CP84 | 73 | HepG2 HeLa Caco-2 | 2.3 7.2 >10 | [14,19] |
Type of Modification | Bt Toxin | Target Insect | Increase or Decrease in Toxicity | Reference |
---|---|---|---|---|
Domain exchanges | ||||
Domain III Exchange For Domain III of Cry1Ab. | mCry3Aa | Diabrotica virgifera | The toxicity increased ≥19%. | [58] |
Domain III, II, I Exchange For Domains of Cry1Ac. | Cry9Aa | Helicoverpa armigera | The toxicity increased between 4.9 and 5.1 times, concerning parentals. | [59] |
Domain III Exchange For Domain III of Cry1Ca. | Cry1Ab; Cry1Ac; Cry1Ba; Cry1Ea; Cry1Fa | Spodoptera exigua | Increased up to 5.5 times for Cry1Fa. | [60] |
Domain III Exchange For Domain III of Cry1CAc | Cry1Ca; Cry1Fb; Cry1Ba; Cry1Da; Cry1Ea | Heliothis virescens | The toxicity increased 172 and 69.6 times more for Cry1Ca and Cry1Fb, respectively. | [61] |
Domain exchanges of Domains II and III, between Cry1Ia and Cry1Ba. | Cry1Ia; Cry1Ba | Leptinotarsa decemlineata | The toxicity increased up to 1127 and 4.2 times, compared to Cry1Ba and Cry1Ia, correspondingly. | [62] |
Site-directed mutagenesis | ||||
Loops 1, 2, and 3, domain II substitution. | Cry4Ba | Culex pipiens; Culex quinquefasciatus | The toxicity increased up to 700 times. | [63] |
Loops 1 and 2 domain II substitution | Cry19Aa | Aedes aegypti | The toxicity increased up to 42,000 times, concerning the parental. | [64] |
Substitution in the domain II | Cry2Ab | Anopheles gambiae | The toxicity increased up to 6.75 times. | [65] |
Loops 1 and 2 domain II substitution and deletions. | Cry1Aa | Culex pipiens | Change in insect target. | [66] |
Substitution in the domain III | Cry1Ab | Spodoptera frugiperda | The toxicity increased up to 44 times, correspondingly to the parental. | [67] |
Truncated toxins | ||||
Truncation and selection of mutants, derived from a phage library | Cry1Ia | Telchin licus | The toxicity increased, showing mortality of 50% for approach. | [68] |
Helix α-1 domain I truncation. | Cry1A | Pectinophora gossypiella | The toxicity increased up to 100 and 150 times for Cry1Ab and CryAc, respectively. | [69] |
Helix α-1 domain I truncation. | Cry1A | Plutella xylostella; Ostrinia nubilalis | The toxicity increased ≥350 times, against resistant insects. | [70] |
C-terminal truncation | Cry1C | Spodoptera exigua | The toxicity increased up to 4 times. | [71] |
Phage-display library | ||||
Selection of mutant toxins from a phage-display library based on their potential of binding. | Cry1Aa | Bombyx mori | Increased the receptor affinity potential up to 16 and 50 times more, contrasting the parentals. | [72] |
Selection of mutant toxins from a phage-display library based on their potential of binding. | Cry8Ka | Anthonomus grandis | Increased the toxicity up to 3.2 times, contrasting the parental. | [73] |
Selection of mutant toxins from a phage-display library based on their potential of binding in the domain II. | Cry1Aa | Nilaparvata lugens | The toxicity increased between 1.4 and 8.9 times, concerning parentals. | [74] |
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Suárez-Barrera, M.O.; Visser, L.; Rondón-Villarreal, P.; Herrera-Pineda, D.F.; Alarcón-Aldana, J.S.; Van den Berg, A.; Orozco, J.; Pinzón-Reyes, E.H.; Moreno, E.; Rueda-Forero, N.J. Genetic Modification Approaches for Parasporins Bacillus thuringiensis Proteins with Anticancer Activity. Molecules 2021, 26, 7476. https://doi.org/10.3390/molecules26247476
Suárez-Barrera MO, Visser L, Rondón-Villarreal P, Herrera-Pineda DF, Alarcón-Aldana JS, Van den Berg A, Orozco J, Pinzón-Reyes EH, Moreno E, Rueda-Forero NJ. Genetic Modification Approaches for Parasporins Bacillus thuringiensis Proteins with Anticancer Activity. Molecules. 2021; 26(24):7476. https://doi.org/10.3390/molecules26247476
Chicago/Turabian StyleSuárez-Barrera, Miguel O., Lydia Visser, Paola Rondón-Villarreal, Diego F. Herrera-Pineda, Juan S. Alarcón-Aldana, Anke Van den Berg, Jahir Orozco, Efraín H. Pinzón-Reyes, Ernesto Moreno, and Nohora J. Rueda-Forero. 2021. "Genetic Modification Approaches for Parasporins Bacillus thuringiensis Proteins with Anticancer Activity" Molecules 26, no. 24: 7476. https://doi.org/10.3390/molecules26247476