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Towards Synthetic Gene Circuits with Enhancers: Biology’s Multi-input Integrators

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Reprogramming Microbial Metabolic Pathways

Part of the book series: Subcellular Biochemistry ((SCBI,volume 64))

Abstract

One of the greatest challenges facing synthetic biology is to develop a technology that allows gene regulatory circuits in microbes to integrate multiple inputs or stimuli using a small DNA sequence “foot-print”, and which will generate precise and reproducible outcomes. Achieving this goal is hindered by the routine utilization of the commonplace σ70 promoters in gene-regulatory circuits. These promoters typically are not capable of integrating binding of more than two or three transcription factors in natural examples, which has limited the field to developing integrated circuits made of two-input biological “logic” gates. In natural examples the regulatory elements, which integrate multiple inputs are called enhancers. These regulatory elements are ubiquitous in all organisms in the tree of life, and interestingly metazoan and bacterial enhancers are significantly more similar in terms of both Transcription Factor binding site arrangement and biological function than previously thought. These similarities imply that there may be underlying enhancer design principles or grammar rules by which one can engineer novel gene regulatory circuits. However, at present our current understanding of enhancer structure-function relationship in all organisms is limited, thus preventing us from using these objects routinely in synthetic biology application. In order to alleviate this problem, in this book chapter, I will review our current view of bacterial enhancers, allowing us to first highlight the potential of enhancers to be a game-changing tool in synthetic biology application, and subsequently to draw a road-map for developing the necessary quantitative understanding to reach this goal.

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Abbreviations

NRI:

nitrogen regulation I

RNAP:

RNA polymerase

TF:

transcription factors

TSS:

transcriptional start site

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Authors and Affiliations

  1. Department of Biotechnology and Food Engineering, Technion – Israel Institute of Technology, Haifa, 32000, Israel

    Roee Amit

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  1. Roee Amit
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Correspondence to Roee Amit .

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Editors and Affiliations

  1. , State Key Laboratory, Jiangnan University, Lihu Avenue 1800, Wuxi, 214122, Jiangsu, China, People's Republic

    Xiaoyuan Wang

  2. School of Biotechnology, Jiangnan University, Lihu Avenue 1800, Wuxi, 214122, China, People's Republic

    Jian Chen

  3. , Div. of Life Sciences, King's College London, Stamford Street 150, London, SE1 9NH, United Kingdom

    Peter Quinn

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Amit, R. (2012). Towards Synthetic Gene Circuits with Enhancers: Biology’s Multi-input Integrators. In: Wang, X., Chen, J., Quinn, P. (eds) Reprogramming Microbial Metabolic Pathways. Subcellular Biochemistry, vol 64. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-5055-5_1

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