All biological processes are in some way pH-dependent. Our human bodies, and those of other organisms, need to maintain specific and constant pH regulation in order to function. Changes in pH can have serious biological consequences or, as researchers at the Qingdao Institute of Bioenergy and Bioprocess Technology (QIBEBT), Chinese Academy of Sciences (CAS) recently found, serious benefits.

The findings were published on October 23 in the journal Science Advances.

Cellulosomes are extracellular complexes consisting of multiple enzymes, which are associated with the cell’s surface. The protein molecules dockerin and cohesin, within the cellulosome cellular structure, were the focus of this study.

“Cellulosomes are complex nanomachines in nature and have great values in biofuel production and biotechnology. This study is an example of their complexity and diversity,” said study author Professor Feng Yingang of the Metabolomics Group.

Fig: A pair of protein modules show pH-dependent dual-binding-site switching. Upper panel: the different interaction sites observed by NMR under different pH conditions; Lower panel: the crystal structures of the complex under two pH conditions have different binding-sites. [IMAGE: FENG YINGANG]

Changes in pH within protein functions have previously been shown to result in ‘‘on-off’’ switches, many of which occur naturally and are essential for life processes. Biotechnical innovations can utilize this relevant phenomenon to develop sensors or switches using biomolecules that are pH-dependent.

The latest discovery, on the cellulosome assembly of the bacterium Clostridium acetobutylicum, takes this prospect further by switching between two functional sites, rather than simply switching ‘‘on’’ or ‘‘off’’, which opens additional possibilities.

“Our study not only reveals an elegant example of biological regulation but also provides a new approach for developing pH-dependent protein devices and biomaterials for biotechnological application,” said Feng.

The researchers found that changing the pH from 4.8 to 7.5 results in the cohesin-binding sites on the dockerin molecule switching from one site to the other. This type of switching between two functional sites had not previously been noted for any interaction between proteins.

Nuclear magnetic resonance (NMR) and isothermal titration calorimetry (ITC) were used to describe the distinct features of this interaction. Researchers additionally noted that the affinity, or the attraction between the molecules, was found to change along with the pH. This property is considered unusual when compared to other cohesin-dockerin interactions and is thus far unique to C. acetobutylicum bacteria.

These discoveries, and other like them in the future, can potentially be used to create more complex biological switches in synthetic biology and further developments in the fields of biotechnology.

“Next, we will continue to elucidate the structure and regulation of cellulosomes, which could provide interesting novel discoveries and new strategies to increase the efficiency of lignocellulose-based biofuel production,” Feng said. “Our ultimate goal is to promote sustainable and economical lignocellulose bioconversion and bioenergy production.”

For more information, please contact:

Cheng Jing

E-mail: chengjing@qibebt.ac.cn

Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences

Source: Qingdao Institute of Bioenergy and Bioprocess Technology,

Chinese Academy of Sciences