Synthetic Biology: Tools to Design, Build, and Optimize Cellular Processes

Abstract

The general central dogma frames the emergent properties of life, which make biology both necessary and difficult to engineer. In a process engineering paradigm, each biological process stream and process unit is heavily influenced by regulatory interactions and interactions with the surrounding environment. Synthetic biology is developing the tools and methods that will increase control over these interactions, eventually resulting in an integrative synthetic biology that will allow ground-up cellular optimization. In this review, we attempt to contextualize the areas of synthetic biology into three tiers: (1) the process units and associated streams of the central dogma, (2) the intrinsic regulatory mechanisms, and (3) the extrinsic physical and chemical environment. Efforts at each of these three tiers attempt to control cellular systems and take advantage of emerging tools and approaches. Ultimately, it will be possible to integrate these approaches and realize the vision of integrative synthetic biology when cells are completely rewired for biotechnological goals. This review will highlight progress towards this goal as well as areas requiring further research.

Tuning Gene Expression in Yarrowia lipolytica by a Hybrid Promoter Approach

“…Finally, these results have the biological implication that the expression capacity for promoters (at least in Y. lipolytica) is enhancer limited. In this regard, this approach expands the quantity and quality of parts available for systems biology research (25,49).…”

Downward causation by information control in micro-organisms

“…At the molecular level, functional convergence is likely more common than it was initially thought to be. By looking at cellular functions that are linked to the intrinsic regulatory mechanisms of the bacterial cell as well as the extrinsic physical and chemical environment in which the bacteria live [6], other interesting conserved functional features under TDC by information control are likely in existence, especially at the level of regulatory controlling elements. In the future, it will also be of prime importance to look at functional networks in an evolutionary context to ultimately understand their modularity and possibly how their parts came to be [19].…”

Combinatorial optimization of CO2 transport and fixation to improve succinate production by promoter engineering

“…A wide array of expression capacities is required since the optimal expression level is likely gene specific and could vary by several orders of magnitude. To address this issue, promoter engineering including promoter library construction and characterization is essential for generating the dynamic range necessary to enable fine-tuned gene expression (Keasling, 2012;Young and Alper, 2010), and it has become an important solution to optimal expression of genes and combinatorial optimization of metabolic pathways (Dahl et al, 2013;Du et al, 2012;Liu et al, 2014). In E. coli, promoter engineering has been successfully applied to optimize single gene expression to improve the synthesis of succinic acid (Tan et al, 2013;Thakker et al, 2011).…”