“Vigyan Patrika” is a series of author interviews hosted by Bio Patrika. Mr. Chatterjee is currently a PhD student in the lab of Dr. Dibyendu Das (Swarnajayanti Fellow 2020) in the Department of Chemical Sciences at the 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).
Author interivew
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 reactions, such as oxidation of fuels and the convergence of diverse products, must have helped in the emergence of complex products, which were connected mutually to further evolve into modern-day reaction networks.
In this context, our work, published in Angew. Chem. Int. 2020, foreshadowed the evolutionary pathways of chemical reaction networks by taking simple biologically relevant molecules and minimal short peptide-based paracrystalline amyloids. This provides a strategy to construct simple cascade reactions, multistep chain reactions, and complex convergence cascades. We harnessed the catalytic potential of short peptide-based paracrystalline amyloid nanotubes from the sequence Im-KLVFFAL (Im-KL), which has binding capability towards a peroxisomal enzyme, sarcosine oxidase (SOX), and a small molecular cofactor, hemin, to develop a platform for facilitating 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, first, SOX bound on the nanotube surface generates hydrogen peroxide (H₂O₂) through aerobic oxidation of sarcosine. The produced H₂O₂ then acts as a substrate for hemin bound to nanotubes to catalyze the oxidation of guaiacol to a brown-colored tetraguaiacol product (Figure 1a). We also exploited the intrinsic hydrolase activity of the imidazole-exposed amyloid surfaces as part of a three-step biocatalytic cascade. For this, we used methyl ester of sarcosine, which was expected to be hydrolyzed by the imidazole-containing amyloid nanotubes to produce sarcosine.
Subsequently, in the second step, aerobic oxidation of sarcosine by enzyme-bound amyloid nanotubes produces glycine and H₂O₂. In the third step of the cascade, the H₂O₂ is consumed by the hemin-bound nanotubes to oxidize guaiacol to tetraguaiacol (Figure 1b). Finally, for a complex convergent cascade, sarcosine and guaiacol were coupled via an ester bond to produce sarcosine guaiacol ester. We expected nanotubes to hydrolyze the activated bond to generate sarcosine and guaiacol (Figure 1c). Then, aerobic oxidation of sarcosine in the presence of SOX-bound Im-KL drives the formation of glycine and H₂O₂. This in-situ generated H₂O₂ converges with guaiacol to form the product, representing a convergent cascade reaction. We found that this ester molecule cascaded to the product in the presence of Im-KL-SOX-hemin, confirmed by a visible color change within 30 seconds (Figure 1d). These can be exploited to create complex logic networks to understand the essence of convergent cascades, often seen in natural systems like protein signaling and cellular transductions.
“[…] 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 understanding chemical evolution. Simple short peptides assembling in harsh conditions and forming structures capable of asymmetric catalysis can help us understand protein evolution. This can help fill critical gaps in our understanding of how extant enzymes developed their specific binding proficiencies. Furthermore, this work can be extended to pharmaceutical industries where multistep one-pot reactions are highly valuable. Industries dealing with agricultural products, specialty chemicals, etc., seek alternative, more accessible ways to synthesize complex products efficiently. In the context of green chemistry, our outcome is significant as we aim to avoid volatile organic solvents and explore environmentally benign routes. Our systems, derived from biological precursors, can perform reactions in aqueous environments, even with hydrophobic substrates.
What was the exciting moment (eureka moment) during your research?
When I get preliminary results that completely draw me into the work — that’s the eureka moment. However, turning an initial result into a well-defined study is no easy task. It requires a targeted approach and sustained effort to reach that breakthrough moment.
What do you hope to do next?
Our next goal is to create reaction networks that can adjust to harsh conditions through cellular information processing, signal sensing, adaptive changes, and communication with other cascade products. These networks could reflect basic evolutionary requirements for survival.
Where do you seek scientific inspiration?
Inspiration is a chaotic yet fascinating obsession for a researcher. What often drives me is a sense of being chased by specific anxieties or pushed by a feeling of urgency. These mental states stimulate my work and transform it into a reliable source of intellectual pleasure.
How do you intend to help Indian science improve?
To project a country as powerful, it’s not just about GDP but also about the strength of scientific innovations and research infrastructure. Belief in the system, right attitudes, and values are key to the excellence of scientific research. Fundamental research helps improve scientific understanding for predicting natural phenomena, while applied research uses those ideas to develop techniques and technologies for human advancement. I aim to promote a scientific environment where both fundamental and applied research can thrive together to elevate the country’s scientific status.
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.
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