Write-up of research and development interests/focus, past and present goals:
Enantiomers in optically pure forms are essentially needed for the better therapeutic efficacy of drugs and pharmaceuticals. These enantiomers may be the end product of either chemical or microbial transformation. My research interest was to resolve the racemic mixture of complex molecule into enantiomerically pure form by bio-transformation. Being the safest and environment friendly route, my focus was to bio-transform the 5’-substituted hydantoin derivatives into optically pure either D- or L-amino acids, which are side chains/intermediates/feedstock of semi-synthetic antibiotic, artificial sweeteners, immuno-suppresive agents, food additives, etc. As a team member, we have successfully completed the industry sponsored project with DSM, Netherlands in 2001 for screening of hydantoinases and carbamoylases required for chiral resolution of 5-substituted hydantoin derivatives into enantiomerically pure form of amino acids. Later the efforts were continued for screening more hydantoinases and carbamoylases as well as bioactive compounds from microbial diversity.
The current interest is exploitation of microbial diversity explored from untouched niches in various parts of India for new antibiotic, substitute for existing antibiotic, enzyme inhibitors, etc. It has been emphasized that exploration and exploitation of the microbial diversity that exists in any country is essential for its Industrial and economic progress. Microbial products have been intrinsic parts of our life since times immemorial. But on the other hand, we have also become susceptible to many deleterious properties of microorganisms that are difficult to cure. Curiously enough, microorganisms themselves have given us the means (antibiotics) to combat many of these diseases, but have continued to further evolve/mutate to become resistant to the curative process. The present focus is to find out an alternative for combating the resistance especially against methicillin resistant Staphylococcus aureus (MRSA)
The rate of drug discovery is much slower than discovery of new antibiotic. Antibiotic resistance developes once it is introduced for therapeutic applications. So, it has become mandatory to find out the alternate way to combat drug resistance. So, we are looking for enzyme inhibitors as drug adjuvant, efflux pump inhibitor as drug potentiator, cell penetrating peptides as drug enhancer/adjuvant. At present we are looking for extended spectrum beta-lactamase inhibitor in Gram's -ve microrganisms, efflux pump inhibitors in Gram +ve microorganisms such as Mycobacterial species, MRSA, etc. There are several combinations of beta-lactamase inhibitor and beta-lactam antibiotics are available in market to treat the infections caused by Klebsiella sps. and E. coli. But the reports are available which show the resistance has been developed against these combinations. We are trying to solve this serious problem by finding out new alternative.
In addition, drug permeabilization across the membrane to reach the target is one of the cause of developing drug resistance. So, we are looking for different aspects such as efflux pump inhibitor, cell penetrating peptides, etc. to reduce the drug resistance.
Recently we have established the screening for antifungal agents, as per international guidelines. There is hardly any antifungal agent available which can be given systemically and less toxic. So, our target is to find out the antifungal agents against C. albicans which has developed drug resistance to second and third generation antifungal agents.
If we ask our-self that is it possible. The answer is Yes because If one considers that approximately 50,000 bioactive and non-bioactive molecules are present in the currently known 5% of culturables that we have studied, then the potential of undiscovered metabolites for genes, proteins, metabolic pathways in the remaining 95% is truly mind boggling! Even from the 5% of culturables the entire metabolite capacity has not been fully explored. In addition, it is known that less than one part of the earth soil has been screened for actinomycetes, the major source for new antibiotics! Bioinformatic tools and databases have added new dimension to drug discovery and it is quite possible to generate synthetic or semisynthetic analogue library to find out better drug candidate compare to natural metabolite for better therapeutic efficiency & phramacological activity.
Selected list of Publications and Patents:
1. Harmandeep K Randhawa, Kanwarpreet K Hundal, Pallavi N Ahirrao, Sanjay M Jachak, Hemraj S Nandanwar* (2016) Efflux pump inhibitory activity of flavonoids isolated from Alpinia calcarata (Haw.) Roscoe against methicillin-resistant Staphylococcus aureus (Conference paper, Accepted in Biologia)
2. Harmandeep Kaur Randhawa, Ankur Gautam, Minakshi Sharma, Rakesh Bhatia, Grish C. Varshney, Gajendra Pal Singh Raghava and Hemraj Nandanwar* (2016) Cell-Penetrating Peptide and Antibiotic Combination Therapy: A Potential Alternative to Combat Drug Resistance in Methicillin-Resistant Staphylococcus aureus. Appl Microbiol Biotechnol 100 (9), 4073-4083; 10.1007/s00253-016-7329-7
3. Ramakrishna Kuppala, Mugunthan Govindarajan, Rushikesh Tambat, Neeraj Patel, Hemraj Nandanwar,* Kamlesh K. Bhutani, K. P. Ravindranathan Karthaa,* (2015) Synthesis and antibacterial activity of ricinoleic acid glycosides. 1. RSC Adv., 2016,6, 3700-3713; DOI: 10.1039/C5RA20136E
4 KPR Kartha, Ramakrishna Kuppala, Mugunthan Govindrajan, KK Bhutani, Hemraj Nandanwar: Recenoleic acid glycoside compounds as antibacterial agents. (INDIAN PATENT APPL NO. 1885/DEL/2015 dated 23.06.2015)
5. Mohit Tyagi, Nikhil Taxak, Prasad V. Bharatam, Hemraj Nandanwar, K. P. Ravindranathan Kartha (2015) Mechanochemical click reaction as a tool for making carbohydrate-based triazole-linked self-assembling materials (CTSAMs).Carbohydrate Research 407, 137–147
6. Gajendra Pal Singh Raghava, Ankur Gautam, Hemraj Santuji Nandanwar: Cell Penetrating Peptide for Biomolecule Delivery. (INDIAN PATENT APPL NO. 3380DEL2013), Patent application filed on 17 Nov 2013 and final application filed on 17 NOV 2014
7. Ankit Malhotra, Nishat Sharma, Navdezda, Navinder Kumar, Kunzes Dolma, Deepak Sharma, Hemraj S. Nandanwar, Anirban Roy Choudhury (2014) Multi-analytical approach to understand biomineralization of gold using rice bran: a novel and economical route. RSC Advances 4, 39484-39490
8. Somendu K. Roy, Sonika Pahwa, Neela Kumari, Udai C. Agrahari, Kamlesh K. Bhutani, Sanjay M. Jachak,Hemraj Nandanwar* (2013) NorA efflux pump inhibitory activity of coumarins from Mesua ferrea. Fitoterapia 90, 140-150
9. Somendu K. Roy, Neela Kumari, Shiv Gupta, Sonika Pahwa, Hemraj Nandanwar*, Sanjay M. Jachak (2013): 7-Hydroxy-(E)-3-phenylmethylene-chroman-4-one analogues as efflux pump inhibitors against Mycobacterium smegmatis mc2 155. European Journal of Medicinal Chemistry 66, 499-507
10. Hemraj S. Nandanwar*, Rajnikant Prajapati and Gurinder S. Hoondal (2013): (D)-p-Hydroxyphenylglycine production by thermostable D-hydantoinase from newly isolated Brevibacillus parabrevis-PHG1. Biocatalysis & Biotransformation 1, 22-32
11. Hemraj S. Nandanwar*, Rakesh M. Vohra and Gurinder S. Hoondal (2013): Trimeric L-methionine-N-carbamoylase from newly isolated Brevibacillus reuszeri HSN1: a potential biocatalyst for production of L-α-amino acids. Biotechnology and Applied Biochemistry 60(2), 219-230
12. Hemraj S. Nandanwar*, Rakesh M. Vohra and Gurinder S. Hoondal (2013): Enhanced stability of newly isolated trimeric L-methionine-N-carbamoylase from Brevibacillus reuszeri HSN1, by covalent immobilization. Biotechnology and Applied Biochemistry 60(3), 305-315
13. Roy Somendu K., Pahwa Sonika, Nandanwar Hemraj*, Jachak Sanjay M (2012): Phenylpropanoids of Alpinia galanga as efflux pump inhibitors in Mycobacterium smegmatis mc2155. Fitoterapia 83, 1248-1255
14. Sowmya P. Mohandas & Sita Ravikumar, Sumi J Menachery, Gayathri Suseelan ,Sai Shyam Narayanan, Hemraj Nandanwar, Kesavan Madhavan Nampoothiri (2012): Bioactives of Microbes Isolated from Western Ghat belt of Kerala Showed beta-lactamase Inhibition along with Wide Spectrum Antimicrobial Activity. Applied Biochemistry and Biotechnology 167, 1753-1762
15. Pahwa S, Kaur J, Cameotra SS, Nandanwar H and Kaur P (2012): Curing of Multiple Plasmids by EtBr in Acinetobacter baumanii: A Clinical Isolate. J. Adv. Dev. Res. 3(1):82-84,
16. Neeraj Pahuja, Gurinder Singh Hoondal, Sanjeev Kumar Soni and Hemraj S. Nandanwar (2011): Laccase from the fungus Simplicillium sp. GSH 1: Effect of pH and temperature on enzyme activity and stability.Pharmacologyonline 3: 1077-1084
17. Nandanwar HS, Hoondal GS, and Vohra RM. (2005) In: Barredo J. L. (ed.) Microbial Enzymes and Biotransformations. Methods in Biotechnology Series, Vol. 17, Humana Press, Totowa, New Jersey, 91-104.
18. Dipti Sareen, Rakesh Sharma, Hemraj S. Nandanwar and Rakesh M. Vohra (2001): Two step purification of D(-)-specific carbamoylase from Agrobacterium tumefaciens AM 10. Protein Expression Purification 21, 170-175
19. B. Karmakar, R. M. Vohra, H. Nandanwar, P. Sharma, K. G. Gupta and R. C. Sobti (2000): Rapid degradation of ferulic acid via 4-vinylguaiacol and vanillin by a newly isolated strain of Bacillus coagulans. J. Biotechnol. 80, 195-202