Part 1: Bio Patrika interviews Mr. Chatterjee on his thoughts about “Chemical evolution, logic gates and amyloid nanotubes”

Mr. Ayan Chatterjee’s interview with Bio Patrika hosting “Vigyan Patrika”, a series of author interviews. Mr. Chatterjee is currently a PhD student in the lab of Dr. Dibyendu Das (Swarnajayanti Fellow 2020) in the Department of Chemical Sciences of Indian Institute of Science Education and Research (IISER) Kolkata. He published a paper titled “Complex Cascade Reaction Networks via Cross β Amyloid Nanotubes” as the joint first author in Angewandte Chemie Int. journal (2020).

How would you explain your paper’s key results to the non-scientific community?

Throughout millions of years of chemical evolution, nature used its diverse chemical inventory and chemical networks to produce simple and gradually complex molecules. One-pot cascade reaction, such as oxidation of fuels, the convergence of diverse products must have helped in the emergence of complex products which were connected mutually to further evolve to modern days reaction networks.

In this context, our work, published in Angew. Chem. Int. 2020, foreshadowed the evolutionary pathways of the chemical reaction networks by taking simple biologically relevant molecules and minimal short peptide-based para crystalline amyloids. This further provides a strategy to construct simple cascade reactions, multistep chain reactions, and complex convergence cascades. We assimilate the catalytic potential of the short peptide-based paracrystalline amyloid nanotubes from the sequence Im-KLVFFAL (Im-KL), having the binding capability towards a peroxisomal enzyme, sarcosine oxidase (SOX) and a small molecular cofactor, hemin to develop a platform for felicitating diverse cascade reactions. These amyloid-enzyme-hemin nanohybrids display two-step, multistep, and convergent cascades which were further exploited to construct three-input and three-concatenated AND gates.

We created a two-step cascade where at first, SOX bound on the nanotube surface will generate H2O2 through aerobic oxidation of sarcosine. The produced H2O2 will then act as the substrate for hemin bound to nanotubes to subsequently catalyze the oxidation of guaiacol to the brown-colored tetraguaiacol product (Figure 1a). We wanted to exploit the intrinsic hydrolase activity of the imidazole exposed amyloid surfaces as part of the three-step biocatalytic cascade. For this purpose, we used methyl ester of sarcosine which was expected to be hydrolyzed by imidazole containing amyloid nanotubes to produce sarcosine.

Figure 1. Reaction scheme for a) two step cascade b) three step cascade and c) convergent cascade by amyloid nanotube. d) construction of a three concatenated logic gates from biologically relevant inputs.

Subsequently, in the second step, aerobic oxidation of sarcosine by enzyme-bound amyloid nanotube produce glycine and H2O2. In the third step of the cascade, the produced H2O2 will be consumed as a substrate by the hemin bound nanotubes to oxidize GU to tetraguaiacol as the final product (Figure 1b). At last, for creating a complex convergent cascade, the two major components of the cascade, sarcosine and guaiacol were coupled via an ester bond to access sarcosine guaiacol ester. We expected that nanotubes would hydrolyze the activated bond to generate sarcosine and guaiacol (Figure 1c). Next, aerobic oxidation of sarcosine in the presence of SOX bound Im-KL will drive the formation of glycine and H2O2. This in-situ generated H2O2 will converge with guaiacol to form the product, thus representing a convergent cascade reaction. We found out that this ester molecule cascaded to the product in the presence of Im-KL-SOX-hemin, as confirmed from the visible colour change of the medium within 30 s of the reaction. These can be further exploited to create a complex logic network to understand the essence of a convergent cascade, often seen in natural systems such as protein signalling and cellular transductions (Figure 1d).

“[…] work resonates with the tempting consequence of being useful for the fundamental understanding of the chemical evolution.”

What are the possible consequences of these findings for your research area?

The published work resonates with the tempting consequence of being useful for the fundamental understanding of the chemical evolution. Simple short peptides assembling in harsh conditions and accessing structures capable of asymmetric catalysis can indeed help us gather important information about protein evolution. This, in turn, can help us fill the critical gaps that remain in our understanding of the development of extant enzymes and its remarkably specific binding proficiencies. Further, this work can be extended to the use in pharmaceutical industries where one multistep pot reactions are of utmost importance. Industries dealing with agricultural products, speciality chemicals and so forth are always on the lookout for alternative and more accessible routes to synthesize complex products with high efficiency. Notably, in the context of green chemistry, our work’s outcome can be significant as there is an ever-increasing pressure on us to discard the use of volatile organic solvents and look for environmentally benign routes. In this context, our systems will be created from biological precursors and they will have the capability of carrying out reactions in an aqueous environment, despite dealing with hydrophobic substrates.

What was the exciting moment (eureka moment) during your research?

When I get some preliminary results that drive me totally into it, can be referred to as the eureka moment. However, transforming an initial result into a well-defined work is not a bed of roses. You have to have a targeted approach and put a lot of effort to get that eureka moment.

What do you hope to do next?

Our next target is to create reaction networks that can adjust themselves to various harsh conditions by cellular information processing, signal sensing and afterwards adaptive changes and communicating with other cascade products, thus can foreshadow basic evolution requirements for survival.

Where do you seek scientific inspiration?

Inspiration is a chaotic and yet fascinating obsession for a researcher. What often inspires me and more drives me explicitly is the sense of being chased by some particular anxieties or pushed by a thrust of urgency. Such mental states of mine stimulate my work and might even transform a reliable basis of intellectual pleasure.

How do you intend to help Indian science improve?

To project a country powerful, not only the GDP but the robustness of scientific innovations and research facilities make the key difference from others. Belief in the systems, right attitudes and values play a substantial role in determining the eminence of scientific research. In this context, fundamental research is one of the key areas that aims the improvement of scientific understandings for better prediction of natural or other phenomena. In contrast, applied research uses fundamental ideas to develop techniques and diverse technologies that can be used to mediate human development. In the future, I want to promote a scientific ambience where both fundamental innovations, as well as application-based research, can marry and function parallelly to advance the country to new heights.

Reference

Chatterjee A#,Mahato C# and Das D. Complex Cascade Reaction Networks via Cross β Amyloid Nanotubes. Angew. Chem. Int. Ed. (2020), doi:10.1002/anie.202011454. #Equal contribution.

Email: ayan.chatterjee94@gmail.com

Learn more about Dr. Das lab research interests https://www.ddaslab.com/.

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