INTERVIEW WITH DR. PRAFULL RANADIVE
It was our pleasure to interview Dr. Prafull Ranadive (Head of R&D, Organica Biotech). He leads a team of scientists, researchers and biotechnologists and drives research and innovation in all the application areas in Organica. Every accomplishment of his is incredible and has something for each one to take back.
Could you please tell us about your career of last thirty years in the field of Industrial Microbiology, Microbial Products and Fermentation Technology?
Thank you for this question! I have completed 30 fruitful years of my career in the microbial research area. To begin with, Microbiology is a very vast field having varied applications ranging from food to space. I started my career in industrial microbiology by beginning my training in the probiotic fermentation area in Franco-Indian Pharmaceuticals in 1991. Overall, I started with the drug discovery through microbial metabolite that was in 1993 in Hoechst Research Centre which was also the only research center in India working on drug discovery. It had great facilities and I was fortunate enough to get a chance to learn about drug discovery from scratch – what screening models are, how these assays are developed to extract new molecules from microbial metabolites, and finally developing scale up processes for their applications. This initial elaborate experience gave me great insights, and I realized I had found my calling.
At that time, research was focused on drugs extracted from natural substances. Globally, only a few countries were carrying out research in this niche area. I also got an opportunity to work in Hoechst Research Centre’s agricultural discovery department for a year. We developed an infrastructure for molecule screening, a climate chamber: an artificial growing chamber for the plant to study the in vivo activities of the product. In layman terms, it was a very sophisticated version of a greenhouse. We cultivated various plant species, screened our biomolecules for efficacy and for herbicidal/fungicidal activities. The experience is worth mentioning, because even now after 30 years I am working in the same vertical, but am investigating these activities at field level.
Further, I also worked in the area of commercial fermentation when I shifted to RPG Life Sciences. I got to work on almost 13 different products derived from microbial metabolites that were at a commercial stage and I contributed towards their process development.
A major achievement I recall from working at RPG was being a part of the team that launched an anthracycline anticancer compound-Daunomycin by fermentation technology for the first time in India. When you talk about microbial fermentation, it started with the penicillin molecule followed by streptomycin. It evolved with time but in addition to antibiotics, microbial metabolites found applications as immunosuppressive drugs, anti-cancer drugs, cholesterol lowering drugs. We also launched Cyclosporin, an immunosuppressive drug isolated from fungal fermentation and Lovastatin, the first natural cholesterol lowering molecule using fungal fermentation.
Post this, I worked with Piramal Life Sciences (one of the leading drug discovery centers in India at that time which eventually became one of the last standing companies keeping natural products discovery alive) and got 6 discovery patents here. For any active biological agent, the yield in the discovery stage is a very small quantity. We found a novel molecule from microbes, and we patented it. But carrying out the development further requires a staggering number of preclinical trials as part of the drug discovery process. From in-vivo, in-vitro, toxicology assays and animal model testing for efficacy to scale up the microbial process for generating the compound in large quantities for pre-clinical trials, it is quite a challenging task.
I got the opportunity to scale up two novel antibiotic molecules active against drug resistant pathogens and presented the Challenges in Fermentation scale up process for production of new chemical entities in “International Conference on Fermentation Technology, Bioprocess and Cell Culture’ (Bioprocess 2013), held in Kansas City, USA. Another challenging bioprocess which we successfully scaled up at 100L scale. It was collaborative project with NRC, Canada for isolating total polar lipids from archaea to be used as carrier for vaccine development. We used Methanobrevibacter smithii, a strict anaerobic archaea which cannot tolerate even traces of oxygen. Can you imagine how difficult it must have been to grow this microbe under strict anaerobic condition? Designing strict anaerobic bioreactor was unique and quite an interesting experience!
These rich experiences have taught me patience, resilience and the importance of accepting failures as well. Unfortunately, by this time natural products drug discovery research slowed down globally, so I moved from these discoveries to the Biotechnology industry.
You are the Head of R&D Organica Biotech. what are your responsibilities in the company? Can you share with us a few current projects that you currently working on?
Life at Organica has pleasantly surprised me with how much I still have yet to discover about the realm of microbiology, and myself. I lead the Inventions and Innovations Team at Organica Biotech, and we form the heart of the Organization. We are involved in developing eco-friendly products and processes to find solutions to various problems related to Agriculture, Wastewater treatment, solid waste management, Sanitation, Bioremediation and aquaculture. We either develop new products and processes or improve existing products to make it more potent and efficient. I was also responsible for upgrading our DSIR certified laboratory and fermentation pilot plant facility.
Apart from this, we also collaborate with different organizations like universities, institutes, government bodies for research projects and product approvals. You see a product perform at field, but you need to also understand its mechanism at molecular, biochemical or cellular level. This study may also lead to a hypothesis to support claims. So we collaborate with institutes to study these activities and get their unbiased opinion. I am also currently working on enhancing the intellectual property of the company, so we are working on publications and patents. We have 2 patents in line which are already under process.
Can you tell us about the award you received from International Coenzyme Q10 Association in Europe?
Before I talk about the award, I would like the readers to know about Coenzyme Q10 (CoQ10). It is an industrially important molecule in pharmaceutical and cosmeceutical applications. It is an antioxidant that our body produces naturally and our cells use CoQ10 for growth and maintenance. As we age this CoQ10 declines, so it is an indicator molecule of our health. When you ingest statins (cholesterol lowering agents), it inhibits an enzyme common to cholesterol and CoQ10 synthesis. So, this discovery of finding CoQ10 supplements for consumers of statin began a long time ago. Multiple clinical trials are happening over the world to evaluate the efficacy of CoQ10 use for different diseases like cardiovascular, neurodegenerative, diabetes, etc. Apart from its pharma application, it can also be used in anti-aging purposes in cosmeceuticals.
Chemists have tried synthesizing this molecule. In general, the biological route is very tedious, so people have tried exploring the chemical route to produce this. But I believe “microbes are smarter than chemists”. There are few molecules that even chemists can’t synthesize, like Vitamin B12 ; and CoQ10 is also a very typical example of this. Presently a company in Japan is producing this molecule by fermentation. But they have their own proprietary processes and they don’t disclose anything about this. As a result, there is nothing known about this molecule in the scientific and academic community. Through my literature research I knew that this is produced by a prokaryote (bacteria). But I thought why not get this CoQ10 from a eukaryote, which will have more similarity in terms of functionality with humans CoQ10 or a high degree of conservation with a mammalian species.
We took a strain of eukaryotic yeast and tried exploring CoQ10 production through that (not a commercial process). The CoQ10 biosynthetic pathway of this yeast and humans is very similar as opposed to bacterial pathways. Instead of cholesterol the yeast produces ergosterol. I tried developing the resistant mutant of the yeast that was resistant against the statin itself and successively found that while resisting the statin it started overproducing the CoQ10 due to overexpression of regulatory enzyme. This hypothesis attracted the attention to derive inverse metabolic engineering strategy to overproduce pathway metabolites, CoQ10, ergosterol and carotenoids in yeast. We then worked on the process development for yeast fermentation and isolation of CoQ10.
There is a Coenzyme Q10 association (headquarters in Europe) and they promote the molecule’s research. Every alternate year they meet to discuss different activities of CoQ10. They give platform to those conducting clinical trials globally (usually by doctors) to present their data and they generally give a recommendation. Since my work was related to CoQ10, I wrote to them and submitted my abstract on the same. Not only did they appreciate my work, but also decided to incorporate the process of producing CoQ10 in their meeting, and this award was given for this work.
You have worked with multiple big companies from Hoechst to Piramal to RPG life Sciences. what do you think has changed in terms of innovations opportunities and facilities over all these years?
It’s a good question. I have seen a lot changes over a period of time. I have seen many acquisitions and mergers in pharma companies. The natural drug discovery sector that was booming earlier, is now teetering on the verge of non-existence. As for positive changes, there have been upgradations in terms of technology and automation. There have been revolutionary changes taking place in instrumentation and process designing taking into consideration the biosafety. Even in my fermentation field, it began with classical antibiotic fermentation, now we use recombinant DNA technology to produce therapeutic proteins. Going from larger volumes, now we are coming to very smaller volumes of therapeutic protein products. Mammalian cell based fermentation is a new avenue for producing high value products. I feel happy to witness these changes and work amidst them.
When it comes to opportunities for students, the supply and demand has remained constant over the years. Earlier fewer students pursued this field and even the opportunities were limited. Nowadays with multiple fields, opportunities are booming their way. There are options beyond core research, with the evolution of pharma and biotech companies, students can pursue a career in regulatory affairs, patents, quality assurance, bioinformatics, bioanalytical, bio based instrumentation, automation and processes, technical marketing, digital marketing of bio products and so much more.
What do you look for in students right out of universities to become a valuable member of your team how should they prepare?
Basically, Biotechnology is a very vast field, and it’s just not true that one can specialize in only a single area in biotechnology as there are many overlapping interdisciplinary areas and opportunities are unlimited. One really needs to be versatile and smart enough to make the most of available opportunities that interest them. What I see is that candidate should choose their career path which fascinates and inspires them. If they choose what they’re passionate about, opportunities will in turn knock on their doors.
We have MOUs with few Universities and we help Biotech students by giving them an opportunity to conduct their projects for Masters and Doctorate degree. We would be happy to help passionate students who are interested in our field of work and are ready to learn from our experience and eventually add to it.
You have said, “Most academic research does not see the light at the end of tunnel with respect to commercialization and I would like to take this forward in collaboration with academic institutes.” Can you tell us how you guide students and academic institutes with their projects?
Most academic research ends with a publication and at most, a degree awarded to the student. There are academic institutes which carry out high-end applied research having potential industrial applications but it does not translate into a value added product or process.
I wish to see more awareness from educational institutes to urge students to also find commercial value of their research by giving them opportunities to undertake application based projects. To not just develop a novel molecule or process, but to also take the next step of patenting it, finding commercial applicability and scaling it up. I know there are lots of constraints in terms of available funds, getting a right partnership and infrastructure. This could be possible with industrial collaborations and through DBT funding. This will definitely help bridging the gap between academia and industry.
