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Dr. Ataur Rahman: Discovering New Class of Macrolide Antibiotics And Pheromone Application For The Pest Control

This is the eleventh part of the series called `Scientist Says’ where we bring for our readers the significant contributions of young scientists in various fields.

Dr. Mohammed Ataur Rahman completed his B.Sc (H) & M.Sc., chemistry from Jamia Millia Islamia, New Delhi in the year  2003-2008. Dr. Rahman started his research journey in the year 2009 with Dr. Jhillu Singh Yadav ( Bhatnagar fellow and former Director of CSIR-IICT) group in Semiochemical division. After completing his Ph.D in the year 2015 December, he joined as a Research Scientist in one of the pharmaceutical companies in Hyderabad. In the year 2016, he was conferred with Postdoctoral position in the group of Professor Andrew G. Myers, at CCB-department, Harvard University, Boston, USA. He worked with Professor Andrew G. Myers from August 2016 to July 2019. In the year 2019 September, he joined New York University, Abu Dhabi, UAE as a Postdoctoral Research Associate with Professor Alan Richard Healy. Currently, he is working on Asymmetric Synthesis and its application to synthesize Polyketide natural products. Dr. Rahman has published 15 research papers in reputed international scientific journals and he is sharing inventorship in three international patents. He shares his significant research works with Rashida Bakait of India Tomorrow. Here are the excerpts of the interview.

Q. Please briefly explain your research.

Ans. My scientific journey began at CSIR-Indian Institute of Chemical Technology (IICT), Hyderabad. At IICT, my initial research began with the development of eco-friendly cost-effective pest-control method to control the pests in the agricultural field as an alternate method of pest control. These eco-friendly pest-controlled method is called as “Pheromone Technology’’. The “Pheromones” are the mixture of chemicals which are released by the male insect to attract the female partner for mating. The whole idea for this technology was to mimic the exact blend ratio of the particular pheromone compound which is released by the male insect and replacing it with artificial pheromones. With the help of artificial pheromones, the female partner of the insect is attracted and is trapped by specially designed trappers. We have developed pheromones for different types of crops such as sugar cane, cardamom, coconut, brinjal, tomato, paddy, ground nuts, cotton etc. This technology is very popular among farmers in South India especially in Andhra Pradesh, Telangana, Tamilnadu and Kerala.

But my PhD topic was different from the above Pheromone work. I started my Ph.D, with Dr. Jhillu Singh Yadav, he was the former director of my institute, CSIR-IICT. The topic of  my Ph.D was – total synthesis of biologically active natural products- especially macrolide natural product, which is a potent class of compound having several distinct biological activities such as anti-cancer, anti-biotics, anti-inflammatory, immunosuppressants etc. My research was focused on the discovery of new synthesis routes for macrolide anti-biotics. During my Ph.D. I have synthesized more than five different macrolide natural products which are quite useful entities for antibiotics, which can be further studied to find new drug candidates.


Q. What was the objective of your research on natural products?

Ans. The objective of my research was to learn the nature of macrolide natural product and its chemistry for the discovery of new class of compounds which can be a potential antibiotic. In the year 2016, I joined Professor Andrew G. Myers research group as a Postdoctoral Fellow in  the department of chemistry and chemical biology, Harvard University. It helped me to learn more about the biological applications of macrolide. Professor Myers was working on discovery of new macrolide antibiotics, which would be effective against gram positive and gram-negative pathogens. As we all know that Azithromycin is the commercial antibiotics which is mostly used against gram-positive pathogens. The main drawback for the antibiotics is that the bacteria develop its resistant mechanism against the drugs. Therefore, we have to come up with a new drug candidate to kill the resistant bacteria. Keeping these things in mind Professor Myers have set up a Macrolide Pharmaceutical company to study & discover a new class of macrolide antibiotics which can be effective against gram-positive as well as gram-negative pathogens. In 2016, I joined as one of the members of forty scientists who are working on this project. In the span of eight years, the Myers group have synthesized approx. 2100 of new macrolides. Out of 2100 new macrolides, we were lucky to find 100 best drug candidates which successfully passed the phase II clinical trials. I have synthesized over 150 new analogues of macrolides and three compounds out of 150 analogues showed best results. There are five patents for this work and I am sharing inventorship in two patents. We are hoping that this will be the future antibiotics.


Q. When did you begin and complete your research on natural products?

Ans.  I started my doctoral research on natural products in the year 2009. In 2011, I registered my Ph.D in AcSIR- Academy of Scientific and Innovative Research at CSIR-IICT, Hyderabad, under the supervision of Dr. Jhillu Singh Yadav. I completed my Ph.D degree in the year December 2015.

Q.  Can you please list some of the findings of your research works?

Ans. The findings for both the research works are as below:

  1. As we all know chemical pesticides used in agriculture are very toxic and are not ecofriendly as it kills all kinds of insects. Pesticides also contaminate the fruits and vegetables.  Long term use of such chemical pesticides will make land infertile and make nitrogen fixation slow. Therefore, to overcome those environmental issues, the new Pheromone Technology is developed. Pheromone Technology is an ecofriendly method to trap the insects. It is insect specific therefore, it does not disturb those insects which are beneficial to plant for pollination such as honey bee, butterfly, etc. Therefore, with the help of this technology farmers are growing healthy crops in some parts of South India. 
  • We all know currently, at least 700,000 people die each year due to drug-resistant diseases, including 230,000 people who die from multidrug-resistant tuberculosis. More and more common diseases, including respiratory tract infections, sexually transmitted infections and urinary tract infections, are untreatable. Lifesaving medical procedures are becoming much riskier, and our food systems are increasingly precarious. Therefore, the newly discovered macrolide antibiotics will be a potential candidate to reduce the death rate due to multidrug-resistant organisms.


Q. What was the conclusion of your research on antibiotics? 

Ans. The molecular mass of macrolide antibiotic “Azithromycin” is high, more than 650, therefore, it’s very hard for the molecule to penetrate the bacterial cell. The bacterial cell wall consists mainly of peptidoglycan (PG), a mesh of polysaccharide strands. Therefore, it’s very hard for Azithromycin to penetrate the bacterial cell to stop its protein synthesis. To overcome with these issues, we have synthesized new macrolide antibiotics with lower molecular mass by keeping intact its biological activity. The smaller molecular mass macrolide penetrates the bacterial cell and stops the protein synthesis there. Our newly discovered macrolide antibiotic worked successfully against the gram-negative and gram-positive pathogens. I hope that in future, the Macrolide Pharmaceuticals formulates its own molecules as new candidates of antibiotics which will work against the broad spectrum of resistant pathogens which are life threatening.


Q. Any scholarships or awards for your research?

Ans. I received funding from department of biotechnology, New Delhi, India for Ph.D (2009-2015) and Project Associateship. In 2016-2019, I was awarded scholarship from the Harvard University, Boston, USA. Currently, I am working as a Postdoctoral Research Associate and I am receiving scholarship from New York University Abu Dhabi, UAE.


Q.  What challenges did you face?

Ans. Doctor of philosophy is a long process, it requires a lot of patience and motivation. This journey will never be smooth, we have to motivate ourselves by being positive. I started my research in natural product chemistry. Natural products are chiral molecules, their synthesis involved multiple steps and therefore, designing a synthetic route to achieve the target, selection of right reagent and condition for chiral functional group transformation is very important.  In multi-step synthesis, designing a feasible synthetic route, choosing right condition, optimizing synthetic plan of each step with best knowledge of literature reports, revising the synthetic plan is very important. Sometimes, ideas would fail and new strategies needed to be designed to proceed and solve issues. Initially, I had a lot of failure reactions which demotivated me but “be positive’’ attitude helped me a lot to achieve my goals and I could finish more than five natural products’ synthesis during my Ph.D.

Q. How do you think your research works would be beneficial to the industry or society?

Ans. We all know chemistry exists everywhere, human life depends on chemistry. Chemistry has its own subclass organic, inorganic, material, polymer, agricultural, pharmaceuticals etc., each class of chemistry has its own importance for the society. Here, I am talking about my perspective of chemistry, organic chemistry and its synthesis. Organic synthesis has its own benefits for the society with its application ranging from pharmaceuticals, agrochemicals, pheromone chemicals, pesticide industry, dyes, cosmetics, high energy material which are used in defence sector, making diagnostic tools for sugar monitoring, high technology materials used  in mobiles, computer and sensors and in aerospace etc.

The pheromone technology is an ultimate application to control the pests in the agricultural field. It is a green technology, eco-friendly, cost-effective and most reliable. These technologies are widely used worldwide. The pheromone techniques are quite popular in the Europe and America.

The current development on macrolide antibiotics, by our team at Myers Lab in collaboration with Macrolide Pharmaceuticals, will help the society to manage the antibiotic crisis in the coming decade. As per my personal observation, after COVID-19, the next health crisis would be due to antibiotics, and this would be a result of the excessive misuse of antibiotics. It develops its own resistant mechanism and restrict the effectiveness of antibiotics.

Q. Any new research you are working on now?
Ans. After completion of post-doctoral study from Harvard University, I joined New York University, Abu Dhabi, UAE as a Postdoctoral Research Associate with Professor Alan Richard Healy, in the year 2019. My current research focuses on asymmetric synthesis and I am working on finding the new asymmetric methods for the carbon-carbon, carbon-nitrogen, carbon-oxygen and carbon-halogen bond formation. These methods and its synthetic tools will be used for the synthesis of polyketide such as macrolide natural product as a clinical candidate for antibiotics. Our main aim is to use our own developed chemistry and apply them for synthesis of polyketide natural product. After developing these methods, we will use our chemistry to automate the synthesis as the nature does, like biosynthetic pathways. 

Q. How do you think your research can be carried forward?
Ans. Organic synthesis is an art of science. It creates new materials. We all know chemistry exists everywhere, human life totally depends on chemistry. Chemistry has its own subclass and each class is very important for the society. Here, I am talking about Organic Chemistry and its synthesis. Organic synthesis in general has its own advantages for the society with its applications, ranging from pharmaceuticals, agrochemicals, pheromone chemicals, pesticide industry, dyes, cosmetics, high energy materials which is used in defense sector, making diagnostic tools for sugar monitoring. My new finding of new class of macrolides can be studied further to address the real crisis of antibiotics in future.

 
Q. Please give few suggestions to the budding scientists.

Ans. Research is a continuous journey. We have to keep ourselves motivated to achieve goals and reach our destination. We have to be ready to accept the real scientific challenges and try to solve and address those issues. My advice to the young scientists is to be positive and keep learning new scientific techniques which will help answer problems. You have to read a lot and keep yourself updated with the current literature and findings. Do not be upset with the failures, as failures also teach you. All the best for the budding scientists.

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