A man-made ATP-binding protein evolved independent of nature causes abnormal growth in bacterial cells.
Recent advances in de novo protein evolution have made it possible to create synthetic proteins from unbiased libraries that fold into stable tertiary structures with predefined functions. However, it is not known whether such proteins will be functional when expressed inside living cells or how a host organism would respond to an encounter with a non-biological protein. Here, we examine the physiology and morphology of Escherichia coli cells engineered to express a synthetic ATP-binding protein evolved entirely from non-biological origins. We show that this man-made protein disrupts the normal energetic balance of the cell by altering the levels of intracellular ATP. This disruption cascades into a series of events that ultimately limit reproductive competency by inhibiting cell division. We now describe a detailed investigation into the synthetic biology of this man-made protein in a living bacterial organism, and the effect that this protein has on normal cell physiology.
Stomel
Joshua M
JM
Center for BioOptical Nanotechnology, Arizona State University, Tempe, Arizona, United States of America.
Wilson
James W
JW
León
Megan A
MA
Stafford
Phillip
P
Chaput
John C
JC
D000255:Adenosine Triphosphate / Q000737:chemistry*; D002352:Carrier Proteins / Q000737:chemistry*; D002455:Cell Division; D018360:Crystallography, X-Ray / Q000379:methods; D004926:Escherichia coli / Q000378:metabolism*; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D046529:Microscopy, Electron, Transmission / Q000379:methods; D008958:Models, Molecular; D008968:Molecular Conformation; D016366:Open Reading Frames; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D015202:Protein Engineering / Q000379:methods*; D017434:Protein Structure, Tertiary
D002352:Carrier Proteins; D000255:Adenosine Triphosphate