期刊
NATURE BIOTECHNOLOGY
卷 27, 期 5, 页码 465-471出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nbt.1536
关键词
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资金
- National Institutes of Health (NIH) through the NIH Director's Pioneer Award Program [DP1 OD003644]
- National Science Foundation Frontiers in Integrative Biological Research program
- Howard Hughes Medical Institute
- EPSRC [EP/G036004/1] Funding Source: UKRI
- Engineering and Physical Sciences Research Council [EP/G036004/1] Funding Source: researchfish
Engineering artificial gene networks from modular components is a major goal of synthetic biology. However, the construction of gene networks with predictable functions remains hampered by a lack of suitable components and the fact that assembled networks often require extensive, iterative retrofitting to work as intended. Here we present an approach that couples libraries of diversified components ( synthesized with randomized nonessential sequence) with in silico modeling to guide predictable gene network construction without the need for post hoc tweaking. We demonstrate our approach in Saccharomyces cerevisiae by synthesizing regulatory promoter libraries and using them to construct feed-forward loop networks with different predicted input-output characteristics. We then expand our method to produce a synthetic gene network acting as a predictable timer, modifiable by component choice. We use this network to control the timing of yeast sedimentation, illustrating how the plug-and-play nature of our design can be readily applied to biotechnology.
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