Prof. Yogender P. Khasa

Professor

email: yogi110@gmail.com; ypkhasa@south.du.ac.in
Phone: 011-24157369

Area of research: Bioprocess Engineering and Industrial Biotechnology

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Description of Research Expertise

Research interest: Bioprocess Engineering and Industrial Biotechnology

Key words: Recombinant human Interleukins, Growth factors, Therapeutic enzymes and thrombolytics, High cell density cultivation, Pichia cell surface display technology

Description of Research: 

Our laboratory is focused on the large scale production of various proteins of therapeutic importance for clinical applications. The genes encoding asparaginase, scFvs, hTNF-α, hG-CSF, hGM-CSF, hIL-2, hIL-3, hIL-6, hIL-7 and streptokinase have been cloned and expressed in two heterologous systems: E. coli and Pichia pastoris. Expression studies using different signal sequences and fusion partners resulted in the soluble expression of these proteins. Expression in Pichia permitted scale- up in the range of  5L to 50L bioreactor under optimized parameters that helped in achieving upto 300 g/L cell biomass (WCW). The large scale recovery of these biomolecules has been established with their subsequent testing for biological activity using cell culture experiments. The indigenous production process of ULP1 protease has been successfully developed to reduce the overall manufacturing cost of recombinant proteins in soluble form. The bioprocess optimization of therapeutically important recombinant proteins such as streptokinase, hIL-3 and hIL-7 was carried out using the 5l bioreactor, where gram level production of these molecules has been obtained. As long-term goal, we are working towards a comprehensive technology development for these proteins for commercial applications.

Publications:

List of Publications in the last 5 years:

Selected peer-reviewed publications (Best publications in chronological order)

1. Babbal, Mohanty S and Khasa YP (2024) Designing Ubiquitin-like protease 1 (Ulp1) based nano biocatalysts: A promising technology for SUMO fusion proteins. International Journal of Biological Macromolecules, 255: 128258 (In Press) (IF: 8.2) https://doi.org/10.1016/j.ijbiomac.2023.128258
2. Chauhan S, and Khasa YP (2023) Challenges and Opportunities in the Process Development of Chimeric Vaccines. Vaccines, 11(12):1828 (IF: 7.8)  https://doi.org/10.3390/vaccines11121828
3. Kashyap A, Saini K, Saini M, Khasa YP, and Gupta R (2023) Development of a novel Pichia pastoris expression platform via genomic integration of lipase gene for sustained release of methanol from methyloleate. Preparative Biochemistry & Biotechnology 53(1): 64–75 (IF: 2.9)  https://doi.org/10.1080/10826068.2022.2039941
4. Babbal, Mohanty S, Dabburu GR, Kumar M and Khasa YP (2022) Heterologous expression of novel SUMO proteases from Schizosaccharomyces pombe in E. coli: Catalytic domain identification and optimization of product yields. International Journal of Biological Macromolecules. 209: 1001-1019 (IF: 8.2) https://doi.org/10.1016/j.ijbiomac.2022.04.078
5. Dagar VK, Babbal, Mohanty S, and Khasa YP (2022) Effect of N-glycosylation on secretion, stability, and biological activity of recombinant human Interleukin-3 (hIL-3) in Pichia pastoris. 3 Biotech Sep;12(9):221.  (IF: 2.8) https://doi.org/10.1007/s13205-022-03293-1
6. Adivitiya, Babbal, Mohanty S, and Khasa YP (2021) Nitrogen supplementation ameliorates product quality and quantity during high cell density bioreactor studies of Pichia pastoris:  A case study with proteolysis prone streptokinase. International Journal of Biological Macromolecules. 180:760-770 (IF: 8.2) https://doi.org/10.1016/j.ijbiomac.2021.03.021

7. Bhadrecha P, Bala M, Khasa YP, Arshi A, Singh J, Kumar M (2020) Hippophae rhamnoides rhizobacteria exhibit diversified cellulase and pectinase activities. Physiol Mol Biol Plants. 26(5):1075-1085 (IF: 3.5) https://doi.org/10.1007/s12298-020-00778-2
8. Adivitiya, Babbal, Mohanty S, Dagar VK and Khasa YP (2019) Development of a streptokinase expression platform using the native signal sequence of the protein with internal repeats 1 (PIR1) in P. pastoris: gene dosage optimization and cell retention strategies. Process Biochemistry, 83:64–76 (IF: 4.4) https://doi.org/10.1016/j.procbio.2019.05.016
9. Babbal, Adivitiya, Mohanty S and Khasa YP (2019) Bioprocess optimization for the overproduction of catalytic domain of Ubiquitin-like protease 1 (Ulp1) from S. cerevisiae in E. coli Fed-batch culture” Enzyme and Microbial Technology, 120:98-109.  (IF: 3.4) https://doi.org/10.1016/j.enzmictec.2018.10.008
10. Adivitiya, Babbal, Mohanty S and Khasa YP (2018) “Engineering of deglycosylated and plasmin resistant variants of recombinant streptokinase in Pichia pastoris” Applied Microbiology and Biotechnology, 102:10561–10577. (IF: 5.0)  https://doi.org/10.1007/s00253-018-9402-x
11. Dagar VK, and Khasa YP (2018) “Combined effect of gene dosage and process optimization strategies on high-level production of recombinant human Interleukin-3 (hIL-3) in Pichia pastoris fed-batch culture” International Journal of Biological Macromolecules, 108:999-1009 (IF: 8.2) https://doi.org/10.1016/j.ijbiomac.2017.11.008
12. Bindal S, Dagar VK, Saini M, Khasa YP, and Gupta R (2018) “High level extracellular production of recombinant γ-glutamyl transpeptidase from Bacillus licheniformis in Escherichia coli fed-batch culture” Enzyme and Microbial Technology, 116:23-32.  (IF: 3.4) https://doi.org/10.1016/j.enzmictec.2018.05.004

Book Chapters Published

1. Babbal, Adivitiya, Mohanty S and Khasa YP (2018 In press) “Enzymes as therapeutic agents” in A   handbook on high value fermentation products Editors: Saurabh Saran, Vikash Babu, Asha Chaubey by Scrivener Publishing
2. Babbal, Adivitiya and Khasa YP (2017) “MICROBES AS BIOCONTROL AGENTS”   in Probiotics and Plant Health Editors: Vivek Kumar, Dr. Manoj Kumar, Dr. Shivesh Sharma, and Dr. Ram Prasad published by Springer; Chapter 24, Page 507-552.
3. Adivitiya, Dagar VK, and  Khasa YP (2017) “Yeast expression systems: Current status and future prospects”  Yeast Diversity in Human Welfare Editors: Tulasi Satyanarayana & Gotthard Kunze published by Springer; Chapter 9, Page 215-250.
4. Kumar S, Dagar VK, Khasa YP and Kuhad RC (2013) Genetically Modified Microorganisms (GMOs) for Bioremediation in “Biotechnology for Environmental Management and Resource Recovery” published by Springer Chapter 11, Page 191-218.
5. Kuhad RC, Gupta R and Khasa YP (2012) Microbial decolorization of colored industrial effluents. “Microbes in Environmental Management and Biotechnology” published by springer Editors, Satayanarayana T and Johri BN. Chapter 35: Page 787-813.

Awards:

2010   Dr. Y. P. Khasa: Young Scientist Award in “Molecular Microbiology” 2010 by Association of Microbiologists of India (AMI).

Memberships of Professional bodies/Associations:

1. Life member of “Association of Microbiologists of India (AMI)” of Delhi Chapter of AMI (No. 1119 – 2010)
2. Life Member “The Biotech Research Society, India” (LM 1768 )
3. Life Member “Microbiologist Society , India” (MS/LM/986)

Memberships of Professional Bodies/ Associations:

Life member of “Association of Microbiologists of India (AMI)” of Delhi Chapter of AMI (No. 1119 – 2010)

Life Member “The Biotech Research Society, India” (LM 1768 )

Student’s Awards:

2020  Best poster award during International  Conference on Biotechnological Interventions for Societal Development Feb 21-23, 2020 (BioSangam-2020)  at MNNIT Allahabad- 211004 UP, India. Titled “Development of a scalable expression platform for commercially important Ubiquitin-like protease (SUMO protease) in Escherichia coli”

2017  Babbal: Best poster award during National conference (BESCON-2017) on Biological Engineering in 21st century, held at Netaji Subhas Institute of Technology, New Delhi, India from September 8-9, 2017 titled         "High level soluble expression of recombinant hTNF-alpha in fed batch culture of E.coli”.

2016  Adivitiya: First prize in poster presentation titled “Use of the Pichia Expression Platform for high-level expression of Streptokinase in Fed-Batch culture” under the theme of “Indigenous Science and technology, Young Scientists’ Conclave” organized as a part of the India International Science Festival 2016 by the Ministry of Science & Technology, Ministry of Earth Sciences and Vigyan Bharti at at CSIR-National Physical Laboratory (NPL) Campus, New Delhi during 7-11 December, 2016.

2016  Adivitiya: Dr. Rana Memorial Best Poster Award during 57^th annual conference of Association of Microbiologists of India held at Guwahati University, Guwahati, Assam from November 24-27, 2016. Astract No. IM-05 Page No. 237 titled “Expression of bioactive recombinant streptokinase in Pichia pastoris fed-batch culture”.

2013 Vikas Kumar: Platinum Jubilee Best Poster Award (AMI-2013) at 54^th annual conference of Association of Microbiologists of India at MDU Rohtak, between 17-20 November 2013. Abstract No. BTBS-16; Page no. 473 titled “Cloning. expression and purification of human-IL-3 in E. coli”.

Invited Guest Lecture:

Invited Guest Lectures:

1. Invited guest lecture on " Production of Recombinant Therapeutics: Scale up Challenges and Remedies" in "MICROFIESTA-23", an annual fest organized by "MICROCOSMOS", the Microbiology Society of Institute of Home Economics, University of Delhi, on 2^nd November, 2023.
2. Invited guest lecture on "Recombinant Therapeutics Production: Challenges and Remedies" in "Koshika", an annual fest organized by "Antheia", the Botanical Society of Miranda House College, University of Delhi, on 11^th April, 2022.
3. Invited guest lecture on “Recombinant Therapeutics Expression in E. coli: Challenges and Remedies” in UGC-STRIDE workshop on “Microbial Metabolites:Biotechnological Advances” organized by Department of Microbiology, MD University, Rohtak  on 16^th February, 2022.
4. Invited guest lecture on “Bioprocess development strategies for the production of engineered recombinant streptokinase in Pichia pastoris” in International  Conference on Biotechnological Interventions for Societal Development Feb 21-23, 2020 (BioSangam-2020) at Motilal Nehru National Institute of Technology (MNNIT) Allahabad- 211004 UP, India.

5. Invited guest lecture on “Development of bioprocess strategies for the over-production of recombinant therapeutics in Yeast expression system: Streptokinase as a case study” in International  Conference on Molecular Basis of Diseases and Therapeutics (ICMBDT-2019) at Central University of Rajasthan, Kishangarh, Ajmer between March 08-10, 2019.

1. Invited guest lecture on “Engineering of N-glycosylation and plasmin susceptible residues of recombinant streptokinase: Process development and scale-up strategies in Pichia pastoris” in 6^th Annual Bioprocessing India Conference on “Recent advancements & applications in bioprocessing for healthcare, bioenergy and environment” at Indian Institute of Technology, Delhi, Hauz Khas, New Delhi, 110016, India between December 16-18, 2018.
2. Invited guest lecture on “Bioprocess optimization of recombinant therapeutics in methylotrophic yeast P. pastoris : Streptokinase as a model protein” in 58^th Annual conference of AMI titled “Microbes for Sustainable Development: Scope & Applications” at Babashaheb Bhimrao Ambedkar University (A Central University), Lucknow, Uttar Pradesh, India between November 16-19, 2017.
3. Invited guest lecture on “Bioprocess development for the over-production of recombinant Streptokinase in Pichia pastoris” in National conference on Biotechnology: Exploring through Innovations (BETI)-2017" at Central University of Haryana, Mahendergarh, Haryana, between November 13-14, 2017.
4. Invited guest lecture on “High level production of recombinant streptokinase in Pichia pastoris fed-batch fermentation” in International conference on Translational biotechnology “BioSangam 2016” between 4-6^th Febrauary 2016, at Motilal Nehru National Institute of Technology (MNNIT) Allahabad- 211004 UP, India.
5. Invited guest Lecture on “Extracellular production of recombinant Streptokinase in Pichia pastoris” in National seminar on “Recent advances in Agriculture, Biomedical & Environmental Biotechnology” between May 01-02, 2015 at Anand engineering college, Agra.
6. Invited guest Lecture on “High level expression of active recombinant streptokinase in Pichia pastoris” in National conference on Evolving trends in Biotechnology between March 28-30, 2015 at Dr. Harisingh Gour Central University, Sagar, MP-470003.
7. Invited guest Lecture on “Recombinant therapeutics and their expression bottlenecks” in Indo-Italian workshop on food technology and cold chain management” at Amity University, Noida, UP on 26^th-27^th November, 2014
8. Invited guest Lecture on “Recent advancements in bioprocess technology: a case study of recombinant therapeutics expression in E. coli” in National conference on Bioprocess Technology: Basics, Advancements and Challenges (BTBAC 2014) on September 13^th 2014 at Jaipur National University, Jaipur, Rajasthan-302017
9. Invited guest Lecture on “Expression of recombinant therapeutics in Pichia pastoris: Human Interleukin-3 (hIL-3) as a model system” in International conference on “Frontier discoveries and emerging opportunities in Life Sciences” between February 13-15, 2014 at Dr. Harisingh Gour Central University, Sagar, MP-470003.
10. Invited guest Lecture on “Therapeutic Proteins: Expression and their optimization bottlenecks” at Department of Microbiology, Punjab University Chandigarh on 20^th Sept. 2013.
11. Invited Guest Lecture at a training program on “Application of Modern Biotechnological Techniques in Molecular Biology Research” at Indian Veterinary Research Institute (IVRI), Mukteswar, Uttarakhand sponsored by Uttarakhand State Biotechnology Department (USBD) from December 3^rd to 17^th, 2012.
12. Invited lecture in National Science day symposium titled “Recombinant protein expression and optimization strategies” on 28^th Feb. 2011 at University of Delhi South Campus, New Delhi India.
13. Invited Lecture in Nation Conference on Microbial Biotechnology “Microcon 2011: Microbes in the service of society” at Punjab University Chandigarh, January 11-12, 2011.
14. Invited Young Scientist Lecture in 51^st Annual Conference “International Symposium on Recent Advances in Cross-disciplinary Microbiology: Avenues and Challenges & International Workshop on rRNA Sequencing, Phylogeny & Next Generation Genome Sequencing” organized by Association of Microbiologists of India at Birla Institute of Technology (BIT), Mesra, Ranchi December 14-17 2010.