Synthetic biology for pharmaceutical drug discovery

Drug Design, Development and Therapy

Volumn 9, Issue , 2015, Pages 6285-6302

  Trosset, Jean Yves ^a   Carbonell, Pablo ^b,c  

^a The Higher Institute of Biotechnologies of Paris   (France)

^b UNIVERSITY OF MANCHESTER   (United Kingdom)

^c UNIVERSITAT POMPEU FABRA   (Spain)

Author keywords

Drug resistance; Metabolic engineering; Natural products; Plant synthetic biology; Synthetic quorum sensing

Indexed keywords

ALKALOID DERIVATIVE; ANTIBIOTIC AGENT; ANTIFUNGAL AGENT; ANTIINFECTIVE AGENT; ANTINEOPLASTIC AGENT; APTAMER; B CELL ANTIGEN RECEPTOR; ERYTHROMYCIN; HYPOCHOLESTEROLEMIC AGENT; IMMUNOSUPPRESSIVE AGENT; LYMPHOCYTE ANTIGEN RECEPTOR; NATURAL PRODUCT; PACLITAXEL; POLYKETIDE; RIBOZYME; TERPENOID DERIVATIVE; TRANSCRIPTION FACTOR; UNCLASSIFIED DRUG; BIOLOGICAL PRODUCT;

BACTERIAL METABOLISM; CELL BASED SCREENING ASSAY; CELL COMMUNICATION; CELL COMPARTMENTALIZATION; CELL PROLIFERATION; CELL SURVIVAL; CHEMICAL ANALYSIS; CHEMICAL DIVERSITY; CYTOTOXICITY; DEGENERATIVE DISEASE; DNA DAMAGE; DRUG MECHANISM; DRUG RESEARCH; DRUG SCREENING; DRUG STRUCTURE; DRUG SYNTHESIS; HIGH THROUGHPUT SCREENING; HOST PATHOGEN INTERACTION; HUMAN; IMMUNOPATHOLOGY; MALIGNANT NEOPLASTIC DISEASE; METABOLIC DISORDER; METABOLIC ENGINEERING; NONHUMAN; OSMOLARITY; PHENOTYPE; PHYSICAL CHEMISTRY; PROTEIN ENGINEERING; PROTEIN FOLDING; QUORUM SENSING; REVIEW; RIBOSWITCH; SITE DIRECTED MUTAGENESIS; SYNTHETIC BIOLOGY; BACTERIUM; CHEMISTRY; CYTOLOGY; DRUG DEVELOPMENT; DRUG EFFECTS; METABOLISM; TRENDS;

ANTI-BACTERIAL AGENTS; BACTERIA; BIOLOGICAL PRODUCTS; DRUG DISCOVERY; HUMANS; PROTEIN ENGINEERING; SYNTHETIC BIOLOGY;

EID: 84949575568     PISSN: None     EISSN: 11778881     Source Type: Journal    
DOI: 10.2147/DDDT.S58049     Document Type: Review

References (230)

1. Moreno L, Pearson AD. How can attrition rates be reduced in cancer drug discovery? Expert Opin Drug Discov. 2013; 8(4): 363-368.
2. Hu Y, Bajorath J. Monitoring drug promiscuity over time. F1000Res. 2014; 3: 218.
3. Leil TA, Bertz R. Quantitative systems pharmacology can reduce attrition and improve productivity in pharmaceutical research and development. Front Pharmacol. 2014; 5: 247.
4. Ryall KA, Tan AC. Systems biology approaches for advancing the discovery of effective drug combinations. J Cheminform. 2015; 7: 7.
5. Srikanthan A, Ethier J-L, Ocana A, Seruga B, Krzyzanowska MK, Amir E. Cardiovascular toxicity of multi-tyrosine kinase inhibitors in advanced solid tumors: a population-based observational study. PLoS One. 2015; 10(3): e0122735.
6. Medema MH, Kottmann R, Yilmaz P, et al. Minimum information about a biosynthetic gene cluster. Nat Chem Biol. 2015; 11(9): 625-631.
7. Sun H, Liu Z, Zhao H, Ang EL. Recent advances in combinatorial biosynthesis for drug discovery. Drug Des Devel Ther. 2015; 9: 823-833.
8. Atanasov AG, Waltenberger B, Pferschy-Wenzig E-M, et al. Discovery and resupply of pharmacologically active plant-derived natural products: a review. Biotechnol Adv. 2015; 15: S0734-9750.
9. Breitling R, Takano E. Synthetic biology advances for pharmaceutical production. Curr Opin Biotechnol. 2015; 35C: 46-51.
10. Kis Z, Pereira HS, Homma T, Pedrigi RM, Krams R. Mammalian synthetic biology: emerging medical applications. J R Soc Interface. 2015; 12(106): 1000.
11. Lee I, Lehner B, Crombie C, Wong W, Fraser AG, Marcotte EM. A single gene network accurately predicts phenotypic effects of gene perturbation in Caenorhabditis elegans. Nat Genet. 2008; 40(2): 181-188.
12. Khalil AS, Collins JJ. Synthetic biology: applications come of age. Nat Rev Genet. 2010; 11(5): 367-379.
13. Juhas M, Eberl L, Church GM. Essential genes as antimicrobial targets and cornerstones of synthetic biology. Trends Biotechnol. 2012; 30(11): 601-607.
14. Bernardo D, Thompson MJ, Gardner TS, et al. Chemogenomic profiling on a genome-wide scale using reverse-engineered gene networks. Nat Biotechnol. 2005; 23(3): 377-383.
15. Bayer TS. Using synthetic biology to understand the evolution of gene expression. Curr Biol. 2010; 20(17): R772-R779.
16. Harvey CJB, Puglisi JD, Pande VS, Cane DE, Khosla C. Precursor directed biosynthesis of an orthogonally functional erythromycin analogue: selectivity in the ribosome macrolide binding pocket. J Am Chem Soc. 2012; 134(29): 12259-12265.
17. Weissman KJ. Mutasynthesis, uniting chemistry and genetics for drug discovery. Trends Biotech. 2007; 25(4): 139-142.
18. Mulinari S. The specificity triad: notions of disease and therapeutic specificity in biomedical reasoning. Philos Ethics Humanit Med. 2014; 9: 14.
19. Maruta H. From chemotherapy to signal therapy (1909-2009): a century pioneered by Paul Ehrlich. Drug Discov Ther. 2009; 3(2): 37-40.
20. Eder J, Herrling PL. Trends in modern drug discovery. Handbook Experimental Pharmacology. 2015: 1-20.
21. Barot KP, Nikolova S, Ivanov I, Ghate MD. Liquid-phase combinatorial library synthesis: recent advances and future perspectives. Comb Chem High Throughput Screen. 2014; 17(5): 417-438.
22. Sun X, Vilar S, Tatonetti NP. High-throughput methods for combinatorial drug discovery. Sci Transl Med. 2013; 5(205): 205rv1.
23. Diller DJ. The synergy between combinatorial chemistry and high-throughput screening. Curr Opin Drug Discov Devel. 2008; 11(3): 346-355.
24. Koehn FE, Carter GT. Rediscovering natural products as a source of new drugs. Discov Med. 2005; 5(26): 159-164.
25. Harris CJ, Hill RD, Sheppard DW, Slater MJ, Stouten PFW. The design and application of target-focused compound libraries. Comb Chem High Throughput Screen. 2011; 14(6): 521-531.
26. Miduturu CV, Deng X, Kwiatkowski N, et al. High-throughput kinase profiling: a more efficient approach toward the discovery of new kinase inhibitors. Chem Biol. 2011; 18: 868-879.
27. Fedorov O, Niesen FH, Knapp S. Kinase Inhibitor Selectivity Profiling Using Differential Scanning Fluorimetry. Totowa, NJ: Humana Press; 2012.
28. Hu Y, Bajorath J. Quantifying the tendency of therapeutic target proteins to bind promiscuous or selective compounds. PLoS One. 2015; 10(5): e0126838.
29. Hu Y, Gupta-Ostermann D, Bajorath J. Exploring compound promiscuity patterns and multi-target activity spaces. Comput Struct Biotechnol J. 2014; 9: e201401003.
30. Boran ADW, Iyengar R. Systems approaches to polypharmacology and drug discovery. Curr Opin Drug Discov Devel. 2010; 13(3): 297-309.
31. Tang J, Aittokallio T. Network pharmacology strategies toward multi-target anticancer therapies: from computational models to experimental design principles. Curr Pharm Des. 2014; 20(1): 23-36.
32. Lehàr J, Krueger AS, Avery W, et al. Synergistic drug combinations improve therapeutic selectivity. Nat Biotechnol. 2010; 27(7): 659-666.
33. Anighoro A, Bajorath J, Rastelli G. Polypharmacology: challenges and opportunities in drug discovery. J Med Chem. 2014; 57(19): 7874-7887.
34. Xiong A-S, Yao Q-H, Peng R-H, Cheng Z-M. Directed in vitro evolution of reporter genes based on semi-rational design and high-throughput screening. Methods Mol Biol. 2010; 634: 239-256.
35. König H, Frank D, Heil R, Coenen C. Synthetic genomics and synthetic biology applications between hopes and concerns. Curr Genomics. 2013; 14(1): 11-24.
36. Mattern DJ, Valiante V, Unkles SE, Brakhage AA. Synthetic biology of fungal natural products. Front Microbiol. 2015; 6: 775.
37. Newman DJ, Cragg GM. Natural products as sources of new drugs over the 30 years from 1981 to 2010. J Nat Prod. 2012; 75(3): 311-335.
38. Szychowski J, Truchon J-F, Bennani YL. Natural products in medicine: transformational outcome of synthetic chemistry. J Med Chem. 2014; 57(22): 9292-9308.
39. Seyedsayamdost MR, Clardy J. Natural products and synthetic biology. ACS Synth Biol. 2014; 3(10): 745-747.
40. Cummings M, Breitling R, Takano E. Steps towards the synthetic biology of polyketide biosynthesis. FEMS Microbiol Lett. 2014; 351(2): 116-125.
41. Fischbach MA, Walsh CT. Assembly-line enzymology for polyketide and nonribosomal peptide antibiotics: logic, machinery, and mechanisms. Chem Rev. 2006; 106(8): 3468-3496.
42. Li J, Neubauer P. Escherichia coli as a cell factory for heterologous production of nonribosomal peptides and polyketides. N Biotechnol. 2014; 31(6): 579-585.
43. Marahiel MA. Working outside the protein-synthesis rules: insights into non-ribosomal peptide synthesis. J Pept Sci. 2009; 15(12): 799-807.
44. Moses T, Pollier J, Thevelein JM, Goossens A. Bioengineering of plant (tri)terpenoids: from metabolic engineering of plants to synthetic biology in vivo and in vitro. New Phytol. 2013; 200(1): 27-43.
45. Minami H. Fermentative production of plant benzylisoquinoline alkaloids in microbes. Biosci Biotechnol Biochem. 2013; 77(8): 1617-1622.
46. Nakagawa A, Minami H, Kim J-S, et al. Bench-top fermentative production of plant benzylisoquinoline alkaloids using a bacterial platform. Bioeng Bugs. 2012; 3(1): 49-53.
47. Trantas EA, Koffas MAG, Xu P, Ververidis F. When plants produce not enough or at all: metabolic engineering of flavonoids in microbial hosts. Front Plant Sci. 2015; 6(7): 1-16.
48. Donadio S, Staver MJ, McAlpine JB, Swanson SJ, Katz L. Modular organization of genes required for complex polyketide biosynthesis. Science. 1991; 252(5006): 675-679.
49. Caffrey P, Bevitt DJ, Staunton J, Leadlay PF. Identification of DEBS 1, DEBS 2 and DEBS 3, the multienzyme polypeptides of the erythromycin-producing polyketide synthase from Saccharopolyspora erythraea. FEBS Lett. 1992; 304(2-3): 225-228.
50. Walsh CT, Fischbach MA. Natural products version 2. 0: connecting genes to molecules. J Am Chem Soc. 2010; 132(8): 2469-2493.
51. Hertweck C. Decoding and reprogramming complex polyketide assembly lines: prospects for synthetic biology. Trends Biochem Sci. 2015; 40(4): 189-199.
52. Li JW-H, Vederas JC. Drug discovery and natural products: end of an era or an endless frontier? Science. 2009; 325(5937): 161-165.
53. Medema MH, Blin K, Cimermancic P, et al. antiSMASH: rapid identification, annotation and analysis of secondary metabolite biosynthesis gene clusters in bacterial and fungal genome sequences. Nucleic Acids Res. 2011; 39(6): W339-W346.
54. Seyedsayamdost MR. High-throughput platform for the discovery of elicitors of silent bacterial gene clusters. Proc Natl Acad Sci U S A. 2014; 111(20): 7266-7271.
55. Wohlleben W, Mast Y, Muth G, Röttgen M, Stegmann E, Weber T. Synthetic biology of secondary metabolite biosynthesis in actinomycetes: engineering precursor supply as a way to optimize antibiotic production. FEBS Lett. 2012; 586(15): 2171-2176.
56. Doroghazi JR, Albright JC, Goering AW, et al. A roadmap for natural product discovery based on large-scale genomics and metabolomics. Nat Chem Biol. 2014; 10(11): 963-968.
57. Cacho RA, Tang Y, Chooi Y-H. Next-generation sequencing approach for connecting secondary metabolites to biosynthetic gene clusters in fungi. Front Microbiol. 2015; 5(774): 1-16.
58. Leavitt JM, Alper HS. Advances and current limitations in transcript-level control of gene expression. Curr Opin Biotechnol. 2015; 34(3): 98-104.
59. Shao Z, Rao G, Li C, Abil Z, Luo Y, Zhao H. Refactoring the silent spectinabilin gene cluster using a plug and play scaffold. ACS Synth Biol. 2013; 2(11): 662-669.
60. Harvey AL, Edrada-Ebel R, Quinn RJ. The re-emergence of natural products for drug discovery in the genomics era. Nat Rev Drug Discov. 2015; 14(2): 111-129.
61. Luo Y, Cobb RE, Zhao H. Recent advances in natural product discovery. Curr Opin Biotechnol. 2014; 30(12): 230-237.
62. Chiang Y-M, Chang S-L, Oakley BR, Wang CCC. Recent advances in awakening silent biosynthetic gene clusters and linking orphan clusters to natural products in microorganisms. Curr Opin Chem Biol. 2011; 15(1): 137-143.
63. Wu M, Law B, Wilkinson B, Micklefield J. Bioengineering natural product biosynthetic pathways for therapeutic applications. Curr Opin Biotechnol. 2012; 23(6): 931-940.
64. Cobb RE, Wang Y, Zhao H. High-efficiency multiplex genome editing of Streptomyces species using an engineered CRISPR/Cas system. ACS Synth Biol. 2014; 3(12): 1-10.
65. Road TC, Cb C. Polyketide biosynthesis: understanding and exploiting modularity. Philos Trans A Math Phys Eng Sci. 2004; 362(1825): 2671-2690.
66. Mitchell W. Natural products from synthetic biology. Curr Opin Chem Biol. 2011; 15(4): 505-515.
67. Zhang W, Tang Y. Combinatorial biosynthesis of natural products. J Med Chem. 2008; 51(9): 2629-2633.
68. Menzella HG, Carney JR, Santi DV. Rational design and assembly of synthetic trimodular polyketide synthases. Chem Biol. 2007; 14(2): 143-151.
69. Du Y-L, Ryan KS. Expansion of bisindole biosynthetic pathways by combinatorial construction. ACS Synth Biol. 2014; 3(12): 1-7.
70. Schmidt EW, Heemstra JR. Assessing the combinatorial potential of the RiPP cyanobactin tru pathway. ACS Synth Biol. 2015; 4(4): 482-492.
71. Xu Y, Zhou T, Zhang S, et al. Diversity-oriented combinatorial biosynthesis of benzenediol lactone scaffolds by subunit shuffling of fungal polyketide synthases. Proc Natl Acad Sci U S A. 2014; 111(34): 12354-12359.
72. Harvey CJB, Puglisi JD, Pande VS, Cane DE, Khosla C. Precursor directed biosynthesis of an orthogonally functional erythromycin analogue: selectivity in the ribosome macrolide binding pocket. J Am Chem Soc. 2012; 134(29): 12259-12265.
73. Winter JM, Tang Y. Synthetic biological approaches to natural product biosynthesis. Curr Opin Biotechnol. 2012; 23(5): 736-743.
74. Smanski MJ, Bhatia S, Zhao D, et al. Functional optimization of gene clusters by combinatorial design and assembly. Nat Biotechnol. 2014; 32(12): 1241-1252.
75. Xu P, Bhan N, Koffas MA. Engineering plant metabolism into microbes: from systems biology to synthetic biology. Curr Opin Biotechnol. 2012; 24(2): 291-299.
76. Unkles SE, Valiante V, Mattern DJ, Brakhage AA. Synthetic biology tools for bioprospecting of natural products in eukaryotes. Chem Biol. 2014; 21(4): 502-508.
77. Klein J, Heal JR, Hamilton WDO, et al. Yeast synthetic biology platform generates novel chemical structures as scaffolds for drug discovery. ACS Synth Biol. 2014; 3(5): 314-323.
78. Kempinski C, Jiang Z, Bell S, Chappell J. Metabolic engineering of higher plants and algae for isoprenoid production. Adv Biochem Eng Biotechnol. 2015; 148: 161-199.
79. Tholl D. Biosynthesis and biological functions of terpenoids in plants. Adv Biochem Eng Biotechnol. 2015; 148: 63-106.
80. Engler C, Youles M, Gruetzner R, et al. A golden gate modular cloning toolbox for plants. ACS Synth Biol. 2014; 3(11): 839-843.
81. Solé R, Macía J. Synthetic biology: biocircuits in synchrony. Nature. 2014; 508(7496): 326-327.
82. Klavins E. Lightening the load in synthetic biology. Nat Biotechnol. 2014; 32(12): 1198-1200.
83. Ye H, Fussenegger M. Synthetic therapeutic gene circuits in mammalian cells. FEBS Lett. 2014; 588(15): 2537-2544.
84. Lienert F, Lohmueller JJ, Garg A, Silver PA. Synthetic biology in mammalian cells: next generation research tools and therapeutics. Nat Rev Mol Cell Biol. 2014; 15(2): 95-107.
85. Lapique N, Benenson Y. Digital switching in a biosensor circuit via programmable timing of gene availability. Nat Chem Biol. 2014; 10(12): 1020-1027.
86. Singh V. Recent advancements in synthetic biology: current status and challenges. Gene. 2014; 535(1): 1-11.
87. Litcofsky KD, Afeyan RB, Krom RJ, Khalil AS, Collins JJ. Iterative plug-and-play methodology for constructing and modifying synthetic gene networks. Nat Methods. 2012; 9(11): 1077-1080.
88. Brückner K, Schäfer P, Weber E, Grützner R, Marillonnet S, Tissier A. A library of synthetic transcription activator-like effector-activated promoters for coordinated orthogonal gene expression in plants. Plant J. 2015; 82(4): 707-716.
89. Smith MT, Wilding KM, Hunt JM, Bennett AM, Bundy BC. The emerging age of cell-free synthetic biology. FEBS Lett. 2014; 588(17): 2755-2761.
90. War AR, Paulraj MG, Ahmad T, et al. Mechanisms of plant defense against insect herbivores. Plant Signal Behav. 2012; 7(10): 1306-1320.
91. Liu W, Stewart CN. Plant synthetic biology. Trends Plant Sci. 2015; 20(5): 309-317.
92. Lassen LM, Nielsen AZ, Olsen CE, et al. Anchoring a plant cytochrome P450 via PsaM to the thylakoids in Synechococcus sp. PCC 7002: evidence for light-driven biosynthesis. PLoS One. 2014; 9(7): e102184.
93. Ohkawa H, Inui H. Metabolism of agrochemicals and related environmental chemicals based on cytochrome P450s in mammals and plants. Pest Manag Sci. 2015; 71(6): 824-828.
94. Mao G, Seebeck T, Schrenker D, Yu O. CYP709B3, a cytochrome P450 monooxygenase gene involved in salt tolerance in Arabidopsis thaliana. BMC Plant Biol. 2013; 13: 169.
95. Heinig U, Gutensohn M, Dudareva N, Aharoni A. The challenges of cellular compartmentalization in plant metabolic engineering. Curr Opin Biotechnol. 2013; 24(2): 239-246.
96. Lau W, Fischbach MA, Osbourn A, Sattely ES. Key applications of plant metabolic engineering. PLoS Biol. 2014; 12(6): e1001879.
97. Pollier J, Moses T, Goossens A. Combinatorial biosynthesis in plants: a (p)review on its potential and future exploitation. Nat Prod Rep. 2011; 28(12): 1897-1916.
98. Curran KA, Alper HS. Expanding the chemical palate of cells by combining systems biology and metabolic engineering. Metab Eng. 2012; 14(4): 289-297.
99. Keasling JD. Synthetic biology and the development of tools for metabolic engineering. Metab Eng. 2012; 14(3): 189-195.
100. Nielsen J, Keasling JD. Synergies between synthetic biology and metabolic engineering. Nat Biotechnol. 2011; 29(8): 693-695.
101. Stephanopoulos G. Synthetic biology and metabolic engineering. ACS Synth Biol. 2012; 1(11): 514-525.
102. Du J, Shao Z, Zhao H. Engineering microbial factories for synthesis of value-added products. J Ind Microbiol Biotechnol. 2011; 38(8): 873-890.
103. Rajagopal R. Bio-based chemicals: in need of innovative strategies. Chem Wkly. 2012; 2(4): 195-200.
104. Lee SYY, Kim HUU, Park JHH, Park JMM, Kim TYY. Metabolic engineering of microorganisms: general strategies and drug production. Drug Discov Today. 2009; 14(1-2): 78-88.
105. Sun J, Alper HS. Metabolic engineering of strains: from industrial-scale to lab-scale chemical production. J Ind Microbiol Biotechnol. 2014; 42(3): 423-436.
106. Hara KY, Araki M, Okai N, Wakai S, Hasunuma T, Kondo A. Development of bio-based fine chemical production through synthetic bioengineering. Microb Cell Fact. 2014; 13(1): 173-191.
107. Immethun CM, Hoynes-O'Connor AG, Balassy A, Moon TSS. Microbial production of isoprenoids enabled by synthetic biology. Front Microbiol. 2013; 4(75): 1-8.
108. Pfleger BF, Pitera DJ, Smolke CD, Keasling JD. Combinatorial engineering of intergenic regions in operons tunes expression of multiple genes. Nat Biotechnol. 2006; 24(8): 1027-1032.
109. Shiba Y, Paradise EM, Kirby J, Ro D-K, Keasling JD. Engineering of the pyruvate dehydrogenase bypass in Saccharomyces cerevisiae for high-level production of isoprenoids. Metab Eng. 2007; 9(2): 160-168.
110. Djordjevic M, Djordjevic M. A simple biosynthetic pathway for large product generation from small substrate amounts. Phys Biol. 2012; 9(5): 056004-056010.
111. Dueber JE, Wu GC, Malmirchegini GR, et al. Synthetic protein scaffolds provide modular control over metabolic flux. Nat Biotechnol. 2009; 27(8): 5-8.
112. Paddon CJ, Keasling JD. Semi-synthetic artemisinin: a model for the use of synthetic biology in pharmaceutical development. Nat Rev Microbiol. 2014; 12(5): 355-367.
113. Ajikumar PK, Xiao W-H, Tyo KEJ, et al. Isoprenoid pathway optimization for taxol precursor overproduction in Escherichia coli. Science. 2010; 330(6000): 70-74.
114. Lim CGG, Fowler ZL, Hueller T, Schaffer S, Koffas MA. High-yield resveratrol production in engineered Escherichia coli. Appl Environ Microbiol. 2011; 77(10): 3451-3460.
115. Wu J, Liu P, Fan Y, et al. Multivariate modular metabolic engineering of Escherichia coli to produce resveratrol from L-tyrosine. J Biotechnol. 2013; 167(4): 404-411.
116. Baltz RH. Combinatorial biosynthesis of cyclic lipopeptide antibiotics: a model for synthetic biology to accelerate the evolution of secondary metabolite biosynthetic pathways. ACS Synth Biol. 2012; 3(10): 748-758.
117. Walker MC, Thuronyi BW, Charkoudian LK, Lowry B, Khosla C, Chang MCY. Expanding the fluorine chemistry of living systems using engineered polyketide synthase pathways. Science. 2013; 341(6150): 1089-1094.
118. Kehr J-CC, Picchi DG, Dittmann E. Natural product biosyntheses in Cyanobacteria: a treasure trove of unique enzymes. Beilstein J Org Chem. 2011; 7(12): 1622-1635.
119. Uzair B, Tabassum S, Rasheed M, Rehman SF. Exploring marine cyanobacteria for lead compounds of pharmaceutical importance. ScientificWorldJournal. 2012; 2012: 179782.
120. El Gamal AA. Biological importance of marine algae. Saudi Pharm J. 2010; 18(1): 1-25.
121. Dhamankar H, Prather KLJ. Microbial chemical factories: recent advances in pathway engineering for synthesis of value added chemicals. Curr Opin Struct Biol. 2011; 21(4): 488-494.
122. Reimers AC, Goldstein Y, Bockmayr A. Generic flux coupling analysis. Math Biosci. 2015; 262(4): 28-35.
123. Porro D, Branduardi P, Sauer M, Mattanovich D. Old obstacles and new horizons for microbial chemical production. Curr Opin Biotechnol. 2014; 30(12): 101-106.
124. Pleiss J. Protein design in metabolic engineering and synthetic biology. Curr Opin Biotechnol. 2011; 22(5): 611-617.
125. Chen Z, Zeng A-P. Protein design in systems metabolic engineering for industrial strain development. Biotechnol J. 2013; 8(5): 523-533.
126. Eriksen DT, Lian J, Zhao H. Protein design for pathway engineering. J Struct Biol. 2014; 185(2): 234-242.
127. Carbonell P, Trosset J-Y. Computational protein design methods for synthetic biology. Methods Mol Biol. 2015; 1244: 3-21.
128. Abatemarco J, Hill A, Alper HS. Expanding the metabolic engineering toolbox with directed evolution. Biotechnol J. 2013; 8(12): 1397-1441.
129. Fernández-castané A, Fehér T, Carbonell P, Pauthenier C, Faulon J. Computer-aided design for metabolic engineering. J Biotechnol. 2014; 192(12): 302-313.
130. Campodonico MA, Andrews BA, Asenjo JA, Palsson BO, Feist AM. Generation of an atlas for commodity chemical production in Escherichia coli and a novel pathway prediction algorithm, GEM-path. Metab Eng. 2014; 25(10): 140-158.
131. Medema MH, van Raaphorst R, Takano E, Breitling R. Computational tools for the synthetic design of biochemical pathways. Nat Rev Microbiol. 2012; 10(3): 191-202.
132. Carbonell P, Parutto P, Herisson J, Pandit SB, Faulon J-L. XTMS: pathway design in an eXTended metabolic space. Nucleic Acids Res. 2014; 42(7): W389-W394.
133. Feher T, Planson A-GG, Carbonell P, et al. Validation of RetroPath, a computer aided design tool for metabolic pathway engineering. Biotechnol J. 2014; 9(11): 1446-1457.
134. Wu J, Du G, Zhou J, Chen J. Systems metabolic engineering of microorganisms to achieve large-scale production of flavonoid scaffolds. J Biotechnol. 2014; 188(3): 72-80.
135. Xu P, Li L, Zhang F, Stephanopoulos G, Koffas M. Improving fatty acids production by engineering dynamic pathway regulation and metabolic control. Proc Natl Acad Sci U S A. 2014; 111(31): 11299-11304.
136. Afroz T, Beisel CL. Understanding and exploiting feedback in synthetic biology. Chem Eng Sci. 2013; 103(11): 79-90.
137. Fehér T, Libis V, Carbonell P, Faulon J-L. A sense of balance: experimental investigation and modeling of a malonyl-CoA sensor in Escherichia coli. Front Bioeng Biotechnol. 2015; 3(4): 46-60.
138. Michener JK, Thodey K, Liang JC, Smolke CD. Applications of genetically-encoded biosensors for the construction and control of biosynthetic pathways. Metab Eng. 2012; 14(3): 212-222.
139. Zhang QC, Petrey D, Deng L, et al. Structure-based prediction of protein-protein interactions on a genome-wide scale. Nature. 2012; 490(7421): 556-560.
140. Hodgman CE, Jewett MC. Cell-free synthetic biology: thinking outside the cell. Metab Eng. 2012; 14(3): 261-269.
141. Dudley QM, Karim AS, Jewett MC. Cell-free metabolic engineering: biomanufacturing beyond the cell. Biotechnol J. 2014; 10(1): 69-82.
142. Jewett MC, Calhoun KA, Voloshin A, Wuu JJ, Swartz JR. An integrated cell-free metabolic platform for protein production and synthetic biology. Mol Syst Biol. 2008; 4(10): 220-230.
143. Firman K, Evans L, Youell JA. Synthetic biology project-developing a single-molecule device for screening drug-target interactions. FEBS Lett. 2012; 586(15): 2157-2163.
144. Ishino Y, Shinagawa H, Makino K, Amemura M, Nakata A. Nucleotide sequence of the iap gene, responsible for alkaline phosphatase isozyme conversion in Escherichia coli, and identification of the gene product. J Bacteriol. 1987; 169(12): 5429-5433.
145. Ronda C, Pedersen LE, Hansen HG, et al. Accelerating genome editing in CHO cells using CRISPR Cas9 and CRISPy, a web-based target finding tool. Biotechnol Bioeng. 2014; 111(8): 1604-1616.
146. Neggers JE, Vercruysse T, Jacquemyn M, et al. Identifying drug-target selectivity of small-molecule CRM1/XPO1 inhibitors by CRISPR/Cas9 genome editing. Chem Biol. 2015; 22(1): 107-116.
147. Kasap C, Elemento O, Kapoor TM. DrugTargetSeqR: a genomics-and CRISPR-Cas9-based method to analyze drug targets. Nat Chem Biol. 2014; 10(8): 626-628.
148. Zheng J, Jia H, Zheng Y. Knockout of leucine aminopeptidase in Toxoplasma gondii using CRISPR/Cas9. Int J Parasitol. 2015; 45(2-3): 141-148.
149. Citorik RJ, Mimee M, Lu TK. Sequence-specific antimicrobials using efficiently delivered RNA-guided nucleases. Nat Biotechnol. 2014; 32(11): 1141-1145.
150. Zheng W, Thorne N, McKew JC. Phenotypic screens as a renewed approach for drug discovery. Drug Discov Today. 2013; 18(21-22): 1067-1073.
151. Chiba T, Tsuchiya T, Mori R, Shimokawa I. Protein reporter bioassay systems for the phenotypic screening of candidate drugs: a mouse platform for anti-aging drug screening. Sensors (Basel). 2012; 12(2): 1648-1656.
152. Duportet X, Wroblewska L, Guye P, et al. A platform for rapid prototyping of synthetic gene networks in mammalian cells. Nucleic Acids Research. 2014; 42(21): 13440-13451.
153. Keung AJ, Joung JK, Khalil AS, Collins JJ. Chromatin regulation at the frontier of synthetic biology. Nat Rev Genet. 2015; 16(3): 159-171.
154. Fussenegger M, Morris RP, Fux C, et al. Streptogramin-based gene regulation systems for mammalian cells. Nat Biotechnol. 2000; 18(11): 1203-1208.
155. Bagchi Bhattacharjee G, Paul Khurana SM. In vitro reporter assays for screening of chemicals that disrupt androgen signaling. J Toxicol. 2014; 2014(701752): 1-7.
156. McIsaac RS, Oakes BL, Botstein D, Noyes MB. Rapid synthesis and screening of chemically activated transcription factors with GFP-based reporters. J Vis Exp. 2013; 26(81): e51153.
157. Eggeling L, Bott M, Marienhagen J. Novel screening methods-biosensors. Curr Opin Biotechnol. 2015; 35(3): 30-36.
158. Wu X, Chen J, Wu M, Zhao JX. Aptamers: active targeting ligands for cancer diagnosis and therapy. Theranostics. 2015; 5(4): 322-344.
159. Mascini M, Palchetti I, Tombelli S. Nucleic acid and peptide aptamers: fundamentals and bioanalytical aspects. Angew Chem Int Ed Engl. 2012; 51(6): 1316-1332.
160. Reverdatto S, Burz DS, Shekhtman A. Peptide aptamers: development and applications. Curr Top Med Chem. 2015; 15(12): 1082-1101.
161. Cobbert JD, DeMott C, Majumder S, et al. Caught in action: selecting peptide aptamers against intrinsically disordered proteins in live cells. Sci Rep. 2015; 5(3): 9402-9411.
162. Chen L-C, Tzeng S-C, Peck K. Aptamer microarray as a novel bioassay for protein-protein interaction discovery and analysis. Biosens Bioelectron. 2013; 42(4): 248-255.
163. Gibert B, Simon S, Dimitrova V, Diaz-Latoud C, Arrigo A-P. Peptide aptamers: tools to negatively or positively modulate HSPB1(27) function. Philos Trans R Soc Lond B Biol Sci. 2013; 368(1617): 20120075-20120083.
164. Shastri A, McGregor LM, Liu Y, et al. An aptamer-functionalized chemomechanically modulated biomolecule catch-and-release system. Nat Chem. 2015; 7(5): 447-454.
165. Mercer TR, Mattick JS. Structure and function of long noncoding RNAs in epigenetic regulation. Nat Struct Mol Biol. 2013; 20(3): 300-307.
166. Sun H, Zhu X, Lu PY, Rosato RR, Tan W, Zu Y. Oligonucleotide aptamers: new tools for targeted cancer therapy. Mol Ther Nucleic Acids. 2014; 3(8): e182-e196.
167. Guo WM, Kong KW, Brown CJ, et al. Identification and characterization of an eIF4e DNA aptamer that inhibits proliferation with high throughput sequencing. Mol Ther Nucleic Acids. 2014; 3(12): e217-e227.
168. Miller RA, Binkowski BF, Belshaw PJ. Ligand-regulated peptide aptamers that inhibit the 5′-AMP-activated protein kinase. J Mol Biol. 2007; 365(4): 945-957.
169. Reverdatto S, Rai V, Xue J, Burz DS, Schmidt AM, Shekhtman A. Combinatorial library of improved peptide aptamers, CLIPs to inhibit RAGE signal transduction in mammalian cells. PLoS One. 2013; 8(6): e65180-e65195.
170. Bardou C, Borie C, Bickle M, Rudkin BB, Colas P. Peptide aptamers for small molecule drug discovery. Methods Mol Biol. 2009; 535: 373-388.
171. Yeh JT-H, Binari R, Gocha T, Dasgupta R, Perrimon N. PAPTi: a peptide aptamer interference toolkit for perturbation of protein-protein interaction networks. Sci Rep. 2013; 3(1): 1156-1164.
172. Berens C, Groher F, Suess B. RNA aptamers as genetic control devices: the potential of riboswitches as synthetic elements for regulating gene expression. Biotechnol J. 2015; 10(2): 246-257.
173. Chappell J, Takahashi MK, Lucks JB. Creating small transcription activating RNAs. Nat Chem Biol. 2015; 11(3): 214-220.
174. Lünse CE, Scott FJ, Suckling CJ, Mayer G. Novel TPP-riboswitch activators bypass metabolic enzyme dependency. Front Chem. 2014; 2(53): 1-8.
175. Prommana P, Uthaipibull C, Wongsombat C, et al. Inducible knockdown of Plasmodium gene expression using the glmS ribozyme. PLoS One. 2013; 8(8): e73783-e73793.
176. Nelson JW, Plummer MS, Blount KF, Ames TD, Breaker RR. Small molecule fluoride toxicity agonists. Chem Biol. 2015; 22(4): 527-534.
177. Callura JM, Dwyer DJ, Isaacs FJ, Cantor CR, Collins JJ. Tracking, tuning, and terminating microbial physiology using synthetic riboregulators. Proc Natl Acad Sci U S A. 2010; 107(36): 15898-15903.
178. Ye H, Aubel D, Fussenegger M. Synthetic mammalian gene circuits for biomedical applications. Curr Opin Chem Biol. 2013; 17(6): 910-917.
179. Liu Y, Zeng Y, Liu L, et al. Synthesizing and gate genetic circuits based on CRISPR-Cas9 for identification of bladder cancer cells. Nat Commun. 2014; 5(5393): 1-8.
180. Kenderian SS, Ruella M, Gill S, Kalos M. Chimeric antigen receptor T-cell therapy to target hematologic malignancies. Cancer Res. 2014; 74(22): 6383-6389.
181. June CH, Maus MV, Plesa G, et al. Engineered T cells for cancer therapy. Cancer Immunol Immunother. 2014; 63(9): 969-975.
182. Abate-Daga D, Rosenberg SA, Morgan RA. Pancreatic cancer: hurdles in the engineering of CAR-based immunotherapies. Oncoimmunology. 2014; 3(6): e29194-e29197.
183. Huang C-T, Oyang Y-J, Huang H-C, Juan H-F. MicroRNA-mediated networks underlie immune response regulation in papillary thyroid carcinoma. Sci Rep. 2014; 4(9): 6495-6509.
184. Geering B, Fussenegger M. Synthetic immunology: modulating the human immune system. Trends Biotechnol. 2014; 33(2): 65-79.
185. Harumiya S, Yoshino A, Hayashizaki K, Mizuno K, Yakura H, Adachi T. A system for reconstructing B cell antigen receptor signaling in the mouse myeloma J558L cell line. Arch Biochem Biophys. 2013; 533(1-2): 18-24.
186. Weber W, Fussenegger M. Emerging biomedical applications of synthetic biology. Nat Rev Genet. 2012; 13(1): 21-35.
187. Agustín-Pavón C, Isalan M. Synthetic biology and therapeutic strategies for the degenerating brain: synthetic biology approaches can transform classical cell and gene therapies, to provide new cures for neurodegenerative diseases. Bioessays. 2014; 36(10): 979-990.
188. Abil Z, Xiong X, Zhao H. Synthetic biology for therapeutic applications. Mol Pharm. 2015; 12(2): 322-331.
189. Hörner M, Reischmann N, Weber W. Synthetic biology: programming cells for biomedical applications. Perspect Biol Med. 2012; 55(4): 490-502.
190. Forbes NS. Engineering the perfect (bacterial) cancer therapy. Nat Rev Cancer. 2010; 10(11): 785-794.
191. Hörner M, Weber W. Molecular switches in animal cells. FEBS Lett. 2012; 586(15): 2084-2096.
192. Furukawa K, Hohmann S. Synthetic biology: lessons from engineering yeast MAPK signalling pathways. Mol Microbiol. 2013; 88(1): 5-19.
193. Grusch M, Schelch K, Riedler R, et al. Spatio-temporally precise activation of engineered receptor tyrosine kinases by light. EMBO J. 2014; 33(15): 1713-1726.
194. Reiner A, Isacoff EY. Photoswitching of cell surface receptors using tethered ligands. Methods Mol Biol. 2014; 1148: 45-68.
195. Stuber GD, Mason AO. Integrating optogenetic and pharmacological approaches to study neural circuit function: current applications and future directions. Pharmacol Rev. 2013; 65(1): 156-170.
196. Sidor MM. Psychiatry's age of enlightenment: optogenetics and the discovery of novel targets for the treatment of psychiatric disorders. J Psychiatry Neurosci. 2012; 37(1): 4-6.
197. Jeong J-W, McCall JG, Shin G, et al. Wireless optofluidic systems for programmable in vivo pharmacology and optogenetics. Cell. 2015; 162(3): 662-674.
198. Rihel J, Schier AF. Sites of action of sleep and wake drugs: insights from model organisms. Curr Opin Neurobiol. 2013; 23(5): 831-840.
199. Farrell MS, Roth BL. Pharmacosynthetics: reimagining the pharmacogenetic approach. Brain Res. 2013; 1511: 6-20.
200. Whittle AJ, Walsh J, de Lecea L. Light and chemical control of neuronal circuits: possible applications in neurotherapy. Expert Rev Neurother. 2014; 14(9): 1007-1017.
201. Tomasetti C. Drug resistance. Adv Exp Med Biol. 2014; 844: 303-316.
202. Kwan BW, Chowdhury N, Wood TK. Combating bacterial infections by killing persister cells with mitomycin C. Environ Microbiol. In press, 2015.
203. Wood TK, Knabel SJ, Kwan BW. Bacterial persister cell formation and dormancy. Appl Environ Microbiol. 2013; 79(23): 7116-7121.
204. Zakeri B, Lu TK. Synthetic biology of antimicrobial discovery. ACS Synth Biol. 2013; 2(7): 358-372.
205. Kohanski MA, Dwyer DJ, Collins JJ. How antibiotics kill bacteria: from targets to networks. Nat Rev Microbiol. 2010; 8(6): 423-435.
206. Liu C, Krishnan J, Xu XY. Intrinsic and induced drug resistance mechanisms: in silico investigations at the cellular and tissue scales. Integr Biol (Camb). 2015; 7(9): 1044-1060.
207. Thaker MN, Wright GD. Opportunities for synthetic biology in antibiotics: expanding glycopeptide chemical diversity. ACS Synth Biol. 2015; 4(3): 195-206.
208. Saxena A, Mukherjee U, Kumari R, Singh P, Lal R. Synthetic biology in action: developing a drug against MDR-TB. Indian J Microbiol. 2014; 54(4): 369-375.
209. Cheng AA, Ding H, Lu TK. Enhanced killing of antibiotic-resistant bacteria enabled by massively parallel combinatorial genetics. Proc Natl Acad Sci U S A. 2014; 111(34): 12462-12467.
210. Jagmann N, Philipp B. Design of synthetic microbial communities for biotechnological production processes. J Biotechnol. 2014; 184: 209-218.
211. Grosskopf T, Soyer OS. Synthetic microbial communities. Curr Opin Microbiol. 2014; 18: 72-77.
212. Mee MT, Collins JJ, Church GM, Wang HH. Syntrophic exchange in synthetic microbial communities. Proc Natl Acad Sci U S A. 2014; 111(20): E2149-E2156.
213. Mahadevan R, Henson MA. Genome-based modeling and design of metabolic interactions in microbial communities. Comput Struct Biotechnol J. 2012; 3: e201210008.
214. Holm A, Vikström E. Quorum sensing communication between bacteria and human cells: signals, targets, and functions. Front Plant Sci. 2014; 5(309): 1-7.
215. Saeidi N, Wong CK, Lo T-M, et al. Engineering microbes to sense and eradicate Pseudomonas aeruginosa, a human pathogen. Mol Syst Biol. 2011; 7(521): 1-11.
216. Du Y-L, Shen X-L, Yu P, Bai L-Q, Li Y-Q. Gamma-butyrolactone regulatory system of Streptomyces chattanoogensis links nutrient utilization, metabolism, and development. Appl Environ Microbiol. 2011; 77(23): 8415-8426.
217. Wang Y, Ma S. Small molecules modulating AHL-based quorum sensing to attenuate bacteria virulence and biofilms as promising antimicrobial drugs. Curr Med Chem. 2014; 21(3): 296-311.
218. Davis RM, Muller RY, Haynes KA. Can the natural diversity of quorum-sensing advance synthetic biology? Front Bioeng Biotechnol. 2015; 3(30): 1-10.
219. Scutera S, Zucca M, Savoia D. Novel approaches for the design and discovery of quorum-sensing inhibitors. Expert Opin Drug Discov. 2014; 9(4): 353-366.
220. Singh R, Ray P. Quorum sensing-mediated regulation of staphylococcal virulence and antibiotic resistance. Future Microbiol. 2014; 9(5): 669-681.
221. Bhargava P, Collins JJ. Boosting bacterial metabolism to combat antibiotic resistance. Cell Metab. 2015; 21(2): 154-155.
222. Peng B, Su Y-B, Li H, et al. Exogenous alanine and/or glucose plus kanamycin kills antibiotic-resistant bacteria. Cell Metab. 2015; 21(2): 249-261.
223. Lee HH, Collins JJ. Microbial environments confound antibiotic efficacy. Nat Chem Biol. 2012; 8(1): 6-9.
224. Planson A-G, Carbonell P, Grigoras I, Faulon J-L. Engineering antibiotic production and overcoming bacterial resistance. Biotechnol J. 2011; 6(7): 812-825.
225. Zhang Q, Bhattacharya S, Conolly RB, Clewell HJ, Kaminski NE, Andersen ME. Molecular signaling network motifs provide a mechanistic basis for cellular threshold responses. Environ Health Perspect. 2014; 122(12): 1261-1270.
226. Dunlop MJ, Dossani ZY, Szmidt HL, et al. Engineering microbial biofuel tolerance and export using efflux pumps. Mol Syst Biol. 2011; 7(487): 1-7.
227. Planson A-G, Carbonell P, Paillard E, Pollet N, Faulon J-L. Compound toxicity screening and structure-activity relationship modeling in Escherichia coli. Biotechnol Bioeng. 2012; 109(3): 846-850.
228. Oberhardt MA, Yizhak K, Ruppin E. Metabolically re-modeling the drug pipeline. Curr Opin Pharmacol. 2013; 13(5): 778-785.
229. Chakravarti D, Wong WW. Synthetic biology in cell-based cancer immunotherapy. Trends Biotechnol. 2015; 33(8): 449-461.
230. Bacchus W, Aubel D, Fussenegger M. Biomedically relevant circuit-design strategies in mammalian synthetic biology. Mol Syst Biol. 2013; 9: 691.