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Synthetic biology and metabolic engineering.
Literature Information
| DOI | 10.1021/sb300094q |
|---|---|
| PMID | 23656228 |
| Journal | ACS synthetic biology |
| Impact Factor | 3.9 |
| JCR Quartile | Q1 |
| Publication Year | 2012 |
| Times Cited | 72 |
| Keywords | Metabolic Engineering, Synthetic Biology, Metabolic Pathways, Synthetic DNA, Biological Manufacturing |
| Literature Type | Journal Article, Review |
| ISSN | 2161-5063 |
| Pages | 514-25 |
| Issue | 1(11) |
| Authors | Gregory Stephanopoulos |
TL;DR
This paper reviews the evolution of metabolic engineering and synthetic biology, highlighting how metabolic engineering focuses on optimizing microbial pathways for product synthesis, while synthetic biology emphasizes fundamental biological research through synthetic DNA and genetic circuits. It proposes distinct paradigms for each field—unit operations for metabolic engineering and electronic circuits for synthetic biology—underscoring their overlapping yet unique contributions to biomanufacturing and biological research.
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Metabolic Engineering · Synthetic Biology · Metabolic Pathways · Synthetic DNA · Biological Manufacturing
Abstract
Metabolic engineering emerged 20 years ago as the discipline occupied with the directed modification of metabolic pathways for the microbial synthesis of various products. As such, it deals with the engineering (design, construction, and optimization) of native as well as non-natural routes of product synthesis, aided in this task by the availability of synthetic DNA, the core enabling technology of synthetic biology. The two fields, however, only partially overlap in their interest in pathway engineering. While fabrication of biobricks, synthetic cells, genetic circuits, and nonlinear cell dynamics, along with pathway engineering, have occupied researchers in the field of synthetic biology, the sum total of these areas does not constitute a coherent definition of synthetic biology with a distinct intellectual foundation and well-defined areas of application. This paper reviews the origins of the two fields and advances two distinct paradigms for each of them: that of unit operations for metabolic engineering and electronic circuits for synthetic biology. In this context, metabolic engineering is about engineering cell factories for the biological manufacturing of chemical and pharmaceutical products, whereas the main focus of synthetic biology is fundamental biological research facilitated by the use of synthetic DNA and genetic circuits.
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Primary Questions Addressed
- How do the engineering principles of synthetic biology differ from those of metabolic engineering in practical applications?
- What are some specific examples of products synthesized through metabolic engineering that highlight its advantages over traditional methods?
- In what ways can synthetic biology enhance the efficiency of metabolic pathways in microbial systems?
- How do recent advancements in synthetic DNA technology impact the future of both synthetic biology and metabolic engineering?
- What challenges do researchers face when integrating concepts from synthetic biology into metabolic engineering practices?
Key Findings
1. Research Background and Purpose
Metabolic engineering has been a prominent field for two decades, primarily concerned with the deliberate modification of microbial metabolic pathways to synthesize a variety of products. This discipline leverages the principles of synthetic biology, particularly the use of synthetic DNA, to enhance the design, construction, and optimization of both native and non-natural pathways for product synthesis. However, there is a recognized gap in the overlap between metabolic engineering and synthetic biology, particularly concerning their approaches to pathway engineering. This paper aims to clarify the distinctions and commonalities between these two fields and proposes two distinct paradigms that encapsulate their respective focuses.
2. Key Methods and Findings
The authors reviewed the historical evolution of metabolic engineering and synthetic biology, examining how each has developed its methodologies and applications. They identified two paradigms: one for metabolic engineering, likened to unit operations in chemical engineering, emphasizing the engineering of cell factories for the production of chemicals and pharmaceuticals. In contrast, the synthetic biology paradigm is compared to electronic circuits, focusing on fundamental biological research and the manipulation of genetic circuits and synthetic DNA. The paper highlights the various areas of research within synthetic biology, including the fabrication of biobricks, synthetic cells, and the study of nonlinear cell dynamics, although it notes that these do not collectively form a singular, coherent definition of synthetic biology.
3. Core Conclusions
The paper concludes that while metabolic engineering and synthetic biology share a common interest in pathway engineering, their objectives and methodologies are distinct. Metabolic engineering is primarily oriented towards practical applications in biomanufacturing, aiming to optimize microbial systems for the efficient production of valuable compounds. In contrast, synthetic biology is more focused on basic research, exploring the fundamental principles of biology through engineered genetic components and systems. This differentiation suggests that while the two fields can benefit from one another, they serve different roles in the broader landscape of biological research and application.
4. Research Significance and Impact
The insights from this paper have significant implications for both fields. By delineating the unique objectives of metabolic engineering and synthetic biology, researchers can better align their efforts and resources towards specific goals, facilitating advancements in biomanufacturing and synthetic biology applications. This understanding can foster interdisciplinary collaborations, enhance educational approaches, and guide funding and policy decisions in biotechnology. Furthermore, clarifying these distinctions may help in addressing challenges in both fields, ultimately leading to more efficient and innovative solutions in biotechnology and synthetic biology.
Literatures Citing This Work
- Microbial production of isoprenoids enabled by synthetic biology. - Cheryl M Immethun;Allison G Hoynes-O'Connor;Andrea Balassy;Tae Seok Moon - Frontiers in microbiology (2013)
- Semi-synthetic artemisinin: a model for the use of synthetic biology in pharmaceutical development. - Chris J Paddon;Jay D Keasling - Nature reviews. Microbiology (2014)
- Improving industrial yeast strains: exploiting natural and artificial diversity. - Jan Steensels;Tim Snoek;Esther Meersman;Martina Picca Nicolino;Karin Voordeckers;Kevin J Verstrepen - FEMS microbiology reviews (2014)
- Engineering synergy in biotechnology. - Jens Nielsen;Martin Fussenegger;Jay Keasling;Sang Yup Lee;James C Liao;Kristala Prather;Bernhard Palsson - Nature chemical biology (2014)
- Improving fatty acids production by engineering dynamic pathway regulation and metabolic control. - Peng Xu;Lingyun Li;Fuming Zhang;Gregory Stephanopoulos;Mattheos Koffas - Proceedings of the National Academy of Sciences of the United States of America (2014)
- Cofactor engineering for enhancing the flux of metabolic pathways. - M Kalim Akhtar;Patrik R Jones - Frontiers in bioengineering and biotechnology (2014)
- 2-Keto acids based biosynthesis pathways for renewable fuels and chemicals. - Yohei Tashiro;Gabriel M Rodriguez;Shota Atsumi - Journal of industrial microbiology & biotechnology (2015)
- In vivo evolution of metabolic pathways: Assembling old parts to build novel and functional structures. - Alejandro Luque;Sarra C Sebai;Vincent Sauveplane;Odile Ramaen;Rudy Pandjaitan - Bioengineered (2014)
- When plants produce not enough or at all: metabolic engineering of flavonoids in microbial hosts. - Emmanouil A Trantas;Mattheos A G Koffas;Peng Xu;Filippos Ververidis - Frontiers in plant science (2015)
- Optimization of the heme biosynthesis pathway for the production of 5-aminolevulinic acid in Escherichia coli. - Junli Zhang;Zhen Kang;Jian Chen;Guocheng Du - Scientific reports (2015)
... (62 more literatures)
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