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Biological Chemistry

Researchers Transplant Part Of A 24-Hour Biological Clock Into Live Bacteria

Synthetic Biology: Circadian clock proteins from cyanobacteria work inside noncircadian E. Coli

by Sarah Everts
June 12, 2015 | A version of this story appeared in Volume 93, Issue 24

In a synthetic biology first, researchers have transplanted a component of a photosynthetic cyanobacterium’s biological clock into Escherichia coli, a bacterium not known to keep track of time. The feat could enable biological computing and reprogramming of a jet-lagged person’s gut bacteria to align digestion with a new time zone, says Pamela A. Silver of Harvard Medical School in Boston, who led the research (Sci. Adv. 2015, DOI: 10.1126/sciadv.1500358).

“The field of circadian biology has been waiting for this result,” comments Andrew J. Millar of Scotland’s University of Edinburgh. Other teams have engineered synthetic rhythmic circuits into organisms, but this is the first team to transfer part of an existing circadian clock between organisms. It is also the first engineered system to operate on a 24-hour cycle, Millar explains.

To achieve the feat, Silver’s team inserted into E. coli three cyanobacterium genes that code for a biological circuit. In this circadian circuit, one of the proteins, called KaiC, is phosphorylated at night and dephosphorylated during the day. The team also appended KaiC to a subunit of E. coli’s RNA polymerase. Then they capitalized on the fact that phosphorylated KaiC, with RNA polymerase in tow, binds to a region in E. coli’s DNA that activates the production of green fluorescent protein (GFP), which they also engineered into E. coli. The cells produced GFP in tune with KaiC’s 24-hour phosphorylation-dephosphorylation cycle, analogous to a day-night cycle.

Diagram describing how part of a circadian clock in cyanobacteria was transplanted in to E. coli.
Ticktock: Researchers inserted into E. coli a circadian clock circuit from cyanobacteria, composed of three proteins: KaiA, KaiB, and KaiC. The engineered bacteria glowed green periodically, in tune with a 24-hour day-night cycle.


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