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Synthetic biology--putting engineering into biology.

Literature Information

DOI10.1093/bioinformatics/btl469
PMID16954140
JournalBioinformatics (Oxford, England)
Impact Factor5.4
JCR QuartileQ1
Publication Year2006
Times Cited73
KeywordsSynthetic Biology, Engineering-driven, DNA Synthesis, Protein Engineering, Standardization
Literature TypeJournal Article, Review
ISSN1367-4803
Pages2790-9
Issue22(22)
AuthorsMatthias Heinemann, Sven Panke

TL;DR

This paper reviews the advancements in synthetic biology, emphasizing the engineering-driven construction of complex biological systems through artificial gene networks, DNA synthesis, and protein engineering. The findings highlight the potential for practical applications, such as pharmaceutical manufacturing, by integrating engineering principles like standardization and systematic design into the biological synthesis process.

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Synthetic Biology · Engineering-driven · DNA Synthesis · Protein Engineering · Standardization

Abstract

Synthetic biology is interpreted as the engineering-driven building of increasingly complex biological entities for novel applications. Encouraged by progress in the design of artificial gene networks, de novo DNA synthesis and protein engineering, we review the case for this emerging discipline. Key aspects of an engineering approach are purpose-orientation, deep insight into the underlying scientific principles, a hierarchy of abstraction including suitable interfaces between and within the levels of the hierarchy, standardization and the separation of design and fabrication. Synthetic biology investigates possibilities to implement these requirements into the process of engineering biological systems. This is illustrated on the DNA level by the implementation of engineering-inspired artificial operations such as toggle switching, oscillating or production of spatial patterns. On the protein level, the functionally self-contained domain structure of a number of proteins suggests possibilities for essentially Lego-like recombination which can be exploited for reprogramming DNA binding domain specificities or signaling pathways. Alternatively, computational design emerges to rationally reprogram enzyme function. Finally, the increasing facility of de novo DNA synthesis-synthetic biology's system fabrication process-supplies the possibility to implement novel designs for ever more complex systems. Some of these elements have merged to realize the first tangible synthetic biology applications in the area of manufacturing of pharmaceutical compounds.

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Primary Questions Addressed

  1. How can the principles of synthetic biology be applied to improve the efficiency of pharmaceutical manufacturing?
  2. What are the ethical considerations associated with the engineering of biological systems in synthetic biology?
  3. In what ways can computational design enhance the capabilities of synthetic biology beyond traditional methods?
  4. How does the standardization of biological components facilitate the engineering of complex biological systems?
  5. What are some real-world examples of successful applications of synthetic biology in the development of new drugs or therapies?

Key Findings

1. Research Background and Purpose: Synthetic biology is a rapidly evolving field that combines principles of engineering with biological science to design and construct new biological parts, devices, and systems. The purpose of this research is to elucidate how an engineering-driven approach can enhance the development of complex biological entities for innovative applications. This field is motivated by advancements in artificial gene network design, DNA synthesis, and protein engineering, which open new avenues for synthetic biology applications.

2. Main Methods and Findings: The review systematically evaluates the key aspects of engineering principles applied to synthetic biology. It emphasizes a purpose-oriented approach, requiring a comprehensive understanding of scientific principles. The authors highlight the importance of a hierarchical abstraction framework that facilitates the integration of various components, including standardized interfaces for design and fabrication. The application of engineering concepts is illustrated at the DNA level with artificial operations such as toggle switches and oscillators, which enable dynamic control of biological functions. On the protein level, the modular domain structures of proteins allow for recombination akin to Lego blocks, which can be utilized for customizing DNA binding specificities and signaling pathways. Furthermore, the emergence of computational design tools is noted as a means to rationally alter enzyme functionalities. The review also acknowledges that advancements in de novo DNA synthesis are crucial for the practical implementation of these designs, enabling the construction of more intricate biological systems. Notably, the synthesis of pharmaceutical compounds is highlighted as one of the first successful applications of synthetic biology.

3. Core Conclusion: The integration of engineering principles into synthetic biology not only enhances the ability to design and fabricate complex biological systems but also promotes innovation in creating novel biological applications. The systematic approach proposed facilitates precise control over biological functions, paving the way for the development of tailored biotechnological solutions.

4. Research Significance and Impact: The significance of this research lies in its potential to transform how biological systems are engineered, offering a structured methodology that could lead to breakthroughs in various fields, including medicine, agriculture, and bio-manufacturing. By fostering a deeper understanding of biological engineering, this work can drive the development of advanced synthetic biology applications that address pressing global challenges, such as drug production and sustainable manufacturing. The implications of these advancements could have far-reaching effects on health care, environmental sustainability, and industrial biotechnology, ultimately contributing to a more efficient and innovative biotechnological landscape.

Literatures Citing This Work

  1. Systems biology and biological systems diversity for the engineering of microbial cell factories. - Pau Ferrer - Microbial cell factories (2007)
  2. Synthetic biology: promises and challenges. - Luis Serrano - Molecular systems biology (2007)
  3. Recursive construction of perfect DNA molecules from imperfect oligonucleotides. - Gregory Linshiz;Tuval Ben Yehezkel;Shai Kaplan;Ilan Gronau;Sivan Ravid;Rivka Adar;Ehud Shapiro - Molecular systems biology (2008)
  4. Optimization in computational systems biology. - Julio R Banga - BMC systems biology (2008)
  5. Diffusion of synthetic biology: a challenge to biosafety. - Markus Schmidt - Systems and synthetic biology (2008)
  6. Toward minimal bacterial cells: evolution vs. design. - Andrés Moya;Rosario Gil;Amparo Latorre;Juli Peretó;Maria Pilar Garcillán-Barcia;Fernando de la Cruz - FEMS microbiology reviews (2009)
  7. Stability from structure: metabolic networks are unlike other biological networks. - P van Nes;D Bellomo;M J T Reinders;D de Ridder - EURASIP journal on bioinformatics & systems biology (2009)
  8. You're one in a googol: optimizing genes for protein expression. - Mark Welch;Alan Villalobos;Claes Gustafsson;Jeremy Minshull - Journal of the Royal Society, Interface (2009)
  9. Piecing together a puzzle. An exposition of synthetic biology. - Anna Deplazes - EMBO reports (2009)
  10. Robust synthetic biology design: stochastic game theory approach. - Bor-Sen Chen;Chia-Hung Chang;Hsiao-Ching Lee - Bioinformatics (Oxford, England) (2009)

... (63 more literatures)


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