Synthetic biology: applications come of age.

Synthetic biology: applications come of age.
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DOI:
10.1038/nrg2775
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发表时间:
2010-05
期刊:
Nature reviews. Genetics
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其他
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早期的合成生物学设计,即基因触发开关和抑制器,表明调节组件可以被表征和组装,以在生命系统中产生复杂的、受电子启发的行为(例如,记忆存储和计时)。通过对遗传部分和生物构件的表征和组装,已经构建了更多的器件,包括开关、存储元件、振荡器、脉冲发生器、数字逻辑门、过滤器和通信模块。该领域的进步现在允许从小基因网络扩展到更大的生物计划领域,这些计划有望实现广泛的应用,包括生物传感、治疗以及生物燃料、药品和生物材料的生产。合成生物传感电路由结合分析物的敏感元件和动员细胞反应的传感器模块组成。平衡这两个模块涉及到将模块化和专用性设计到各种电路中。生物传感器敏感元件包括环境响应启动子(转录)、RNA适体(翻译)和蛋白质受体(翻译后)。生物传感器转导模块包括工程基因网络(转录)、非编码调控RNA(翻译)和蛋白质信号转导电路(翻译后)。合成生物学对治疗学的贡献包括:用于疾病机制阐明、药物靶标识别、药物发现平台、治疗治疗、治疗给药以及药物生产和获取的工程网络和生物。在生物燃料和药品的微生物生产中,合成生物学通过帮助构建优化的生物合成途径,补充了传统的遗传和代谢工程努力。通过生物合成途径优化代谢通量传统上是通过用强大的、可诱导的启动子驱动途径酶的表达来完成的。新的合成方法包括各种途径组件的快速多样化,合理和模型引导的途径组件组装,以及混合解决方案。合成生物学领域的进展使其能够从小的基因网络扩展到更大的生物计划,这些计划有望实现广泛的应用,包括生物传感、治疗以及生物燃料、药品和生物材料的生产。合成生物学正在将工程师和生物学家聚集在一起,设计和建造新的生物分子组件、网络和途径,并使用这些结构来重新连接和重新编程生物体。这些重新设计的生物体将在未来几年改变我们的生活,导致更便宜的药物、为我们的汽车提供燃料的“绿色”手段,以及用于攻击“超级细菌”和癌症等疾病的靶向疗法。基因电路、生物模块和合成途径的从头工程正在开始解决这些关键问题,并正在用于相关的实际应用。
Early synthetic biology designs, namely the genetic toggle switch and repressilator, showed that regulatory components can be characterized and assembled to bring about complex, electronics-inspired behaviours in living systems (for example, memory storage and timekeeping). Through the characterization and assembly of genetic parts and biological building blocks, many more devices have been constructed, including switches, memory elements, oscillators, pulse generators, digital logic gates, filters and communication modules. Advances in the field are now allowing expansion beyond small gene networks to the realm of larger biological programs, which hold promise for a wide range of applications, including biosensing, therapeutics and the production of biofuels, pharmaceuticals and biomaterials. Synthetic biosensing circuits consist of sensitive elements that bind analytes and transducer modules that mobilize cellular responses. Balancing these two modules involves engineering modularity and specificity into the various circuits. Biosensor sensitive elements include environment-responsive promoters (transcriptional), RNA aptamers (translational) and protein receptors (post-translational). Biosensor transducer modules include engineered gene networks (transcriptional), non-coding regulatory RNAs (translational) and protein signal-transduction circuits (post-translational). The contributions of synthetic biology to therapeutics include: engineered networks and organisms for disease-mechanism elucidation, drug-target identification, drug-discovery platforms, therapeutic treatment, therapeutic delivery, and drug production and access. In the microbial production of biofuels and pharmaceuticals, synthetic biology has supplemented traditional genetic and metabolic engineering efforts by aiding the construction of optimized biosynthetic pathways. Optimizing metabolic flux through biosynthetic pathways is traditionally accomplished by driving the expression of pathway enzymes with strong, inducible promoters. New synthetic approaches include the rapid diversification of various pathway components, the rational and model-guided assembly of pathway components, and hybrid solutions. Advances in the synthetic biology field are allowing an expansion beyond small gene networks towards larger biological programs that hold promise for a wide range of applications, including biosensing, therapeutics and the production of biofuels, pharmaceuticals and biomaterials. Synthetic biology is bringing together engineers and biologists to design and build novel biomolecular components, networks and pathways, and to use these constructs to rewire and reprogram organisms. These re-engineered organisms will change our lives over the coming years, leading to cheaper drugs, 'green' means to fuel our cars and targeted therapies for attacking 'superbugs' and diseases, such as cancer. The de novo engineering of genetic circuits, biological modules and synthetic pathways is beginning to address these crucial problems and is being used in related practical applications.
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