bims-mricoa 2022-05-01 papers

Issue of 2022–05–01
five papers selected by
Merve Yavuz, Bilkent University

Curr Opin Chem Biol. 2022 Apr 25. pii: S1367-5931(22)00036-9. [Epub ahead of print]68 102151

Electrogenetics: Bridging synthetic biology and electronics to remotely control the behavior of mammalian designer cells.

Maysam Mansouri, Martin Fussenegger.

Electrogenetics, the combination of electronics and genetics, is an emerging field of mammalian synthetic biology in which electrostimulation is used to remotely program user-designed genetic elements within designer cells to generate desired outputs. Here, we describe recent advances in electro-induced therapeutic gene expression and therapeutic protein secretion in engineered mammalian cells. We also review available tools and strategies to engineer electro-sensitive therapeutic designer cells that are able to sense electrical pulses and produce appropriate clinically relevant outputs in response. We highlight current limitations facing mammalian electrogenetics and suggest potential future directions for research.

Keywords: Electrogenetics; Electrostimulation; Synthetic biology; Therapeutic cell engineering; Traceless switch control

DOI: https://doi.org/10.1016/j.cbpa.2022.102151

Extreme Mech Lett. 2021 Jul 30. 46 101340

Physical intelligence as a new paradigm.

Metin Sitti.

Intelligence of physical agents, such as human-made (e.g., robots, autonomous cars) and biological (e.g., animals, plants) ones, is not only enabled by their computational intelligence (CI) in their brain, but also by their physical intelligence (PI) encoded in their body. Therefore, it is essential to advance the PI of human-made agents as much as possible, in addition to their CI, to operate them in unstructured and complex real-world environments like the biological agents. This article gives a perspective on what PI paradigm is, when PI can be more significant and dominant in physical and biological agents at different length scales and how bioinspired and abstract PI methods can be created in agent bodies. PI paradigm aims to synergize and merge many research fields, such as mechanics, materials science, robotics, mechanical design, fluidics, active matter, biology, self-assembly and collective systems, to enable advanced PI capabilities in human-made agent bodies, comparable to the ones observed in biological organisms. Such capabilities would progress the future robots and other machines beyond what can be realized using the current frameworks.

Keywords: Physical Intelligence; mechanical computation; mechanical memory; mechanics; meta materials; multistability

Sheng Wu Gong Cheng Xue Bao. 2022 Apr 25. 38(4): 1339-1350

[Advances in synthetic biology of CO2 fixation by heterotrophic microorganisms].

Guipeng Hu, Wei Song, Cong Gao, Liang Guo, Xiulai Chen, Liming Liu.

Human activities increase the concentration of atmospheric carbon dioxide (CO2), which leads to global climate warming. Microbial CO2 fixation is a promising green approach for carbon neutral. In contrast to autotrophic microorganisms, heterotrophic microorganisms are characterized by fast growth and ease of genetic modification, but the efficiency of CO2 fixation is still limited. In the past decade, synthetic biology-based enhancement of heterotrophic CO2 fixation has drawn wide attention, including the optimization of energy supply, modification of carboxylation pathway, and heterotrophic microorganisms-based indirect CO2 fixation. This review focuses on the research progress in CO2 fixation by heterotrophic microorganisms, which is expected to serve as a reference for peaking CO2 emission and achieving carbon neutral by microbial CO2 fixation.

Keywords: CO2 fixation; carbon neutral; carbon peaking; metabolic engineering; synthetic biology

DOI: https://doi.org/10.13345/j.cjb.210627

J Am Chem Soc. 2022 Apr 29.

Turn-on Fluorescent Biosensors for Imaging Hypoxia-like Conditions in Living Cells.

Santiago Guisán-Ceinos, Alexandra R Rivero, Fernando Romeo-Gella, Silvia Simón-Fuente, Silvia Gómez-Pastor, Natalia Calvo, Alejandro H Orrego, José Manuel Guisán, Inés Corral, Francisco Sanz-Rodriguez, Maria Ribagorda.

We present the synthesis, photophysical properties, and biological application of nontoxic 3-azo-conjugated BODIPY dyes as masked fluorescent biosensors of hypoxia-like conditions. The synthetic methodology is based on an operationally simple N═N bond-forming protocol, followed by a Suzuki coupling, that allows for a direct access to simple and underexplored 3-azo-substituted BODIPY. These dyes can turn on their emission properties under both chemical and biological reductive conditions, including bacterial and human azoreductases, which trigger the azo bond cleavage, leading to fluorescent 3-amino-BODIPY. We have also developed a practical enzymatic protocol, using an immobilized bacterial azoreductase that allows for the evaluation of these azo-based probes and can be used as a model for the less accessible and expensive human reductase NQO1. Quantum mechanical calculations uncover the restructuration of the topography of the S1 potential energy surface following the reduction of the azo moiety and rationalize the fluorescent quenching event through the mapping of an unprecedented pathway. Fluorescent microscopy experiments show that these azos can be used to visualize hypoxia-like conditions within living cells.

DOI: https://doi.org/10.1021/jacs.2c01197

ACS Synth Biol. 2022 Apr 25.

Increased Production of Riboflavin by Coordinated Expression of Multiple Genes in Operons in Bacillus subtilis.

Jiajia You, Yuxuan Du, Xuewei Pan, Xian Zhang, Taowei Yang, Zhiming Rao.

Riboflavin is an essential vitamin widely used in the food, pharmaceutical, and feed industries. However, the insufficient supply of precursors caused by the imbalance of intracellular metabolic flow limits the riboflavin synthesis by industrial strains. Here, we increase riboflavin production by tuning multiple gene expression to balance intracellular metabolic flow. First, we tuned the expression of mCherry and egfp genes within operons by generating libraries of tunable intergenic regions (TIGRs) and confirmed the relative expression of the two reporter genes. The TIGR library can coordinate the expression ratio of reporter genes more than 180 times in Escherichia coli and more than 70 times in Bacillus subtilis. Next, we used this strategy to tune the expression of zwf, ribBA, and ywlf genes within operons through the TIGR library to increase the intracellular precursor pool for riboflavin biosynthesis. Based on the fluorescence characteristics of riboflavin, 96-well plates were used to screen the optimal combination mutants quickly. The best-engineered strain was selected from the library, which produced 2.7 g/L riboflavin, increasing by 64.35% in the shake flask. Finally, the riboflavin titer increased by 59.27% to 11.77 g/L in fed-batch fermentation. The strategy described here will contribute to the industrial production of riboflavin and related products by B. subtilis.

Keywords: Bacillus subtilis; PRPP pool; TIGR library; metabolic engineering; riboflavin (VB2)

DOI: https://doi.org/10.1021/acssynbio.1c00640