Indian Institute of Integrative Medicine, Jammu Fermentation Technology Division Overview Fermentation Technology Division focuses on microbial biodiversity research / IPR leading to the production of novel bioactive products, biocatalysts, biotransformed products for human health and enhanced agriculture crop yields through microbial fertilizer, biocides and metal gluconates. This division is well equipped with latest fermentors from lab scale to pilot scale 4KL with supporting downstream processing facilities. molecules. Competencies Isolation, characterization & identification of microbes, screening for specific microbial enzymes and secondary metabolites, enantio/ regiospecific biotransformations. Chemo-profiling of biocatalysts, Biotransformations Multi-functional fermentation scale up facility from lab to pilot scale ranging from 5 to 4000L capacity and downstream processing Technology development for agricultural crop yield increase by biofertilizers, biocontrol agents and micronutrients. Missions and goals Isolation of microbial strains of industrial importance and their characterization for novel bioactive products, biocatalysts for health, agriculture Production of noel bioactives, biocatalysts for health and agriculture from novel endophytes and extremophiles Industrial scale production of microbial enzymes and high value microbial products from wild type and genetically modified strains Biotransformations using free and immobilized enzymes for the production of industrially important Helping Indian industries for scale up of processes and building confidence in Indian industry through transferring technology and training on microbial fermentation processes. Fermentation Technology Division, CSIR-IIIM, Jammu Page 1 Area of research facility from lab scale to pilot scale (54KL capacity) with supporting downstream processing facilities for bacterial, fungal and yeast based products. Isolation of new microorganisms and endophytes to develop library of microorganisms for novel bioactives and biocatalysts. Detailed chemo profiling of enzymes/microorganisms, biotransformations, resolution of chiral drugs/drug intermediates. Endophytes isolation & characterization from selected plants for high value products Identification of microbial strains for various industrially important products/enzymes and their large scale production Biotransformation for industrial process development using microbes/ enzymes and immobilized enzymes for making the bioprocess easy to operate Metabolic engineering of microbes for metabolite production and yields improvement Microbial processes for agriculture crop yield increase through biofertilizers, biocontrol agents and micronutrients Cost effective and environmental friendly processes development for Gluconates (Their use as neutraceuticals, human and veterinary pharmaceuticals, food, cosmetics and crop yields increase) State-of–art equipment required for Microbiology, Enzymology and Bioprocess development Centrifuges ranging from laboratory to industrial scale HPLC GC Current Research Bioprospecting microbial diversity of J&K Microbial strains isolated from various niches of Leh (Ladakh), Drass (Kargil) area (water samples from hot water springs of Chumathong- 16000Ft, Pugga, Nobra 15000Ft and Cold water Lakes of Karzok (Tsomorari 15075 Ft.), Tsoker, Pangong; Soil samples from Karzok 15075Ft, Tanglangla 17500Ft, Changla Pass 17830Ft, Pangong, Nobra (North and south Pullu) 16000-17000Ft, Khurdungla18360Ft. Cataloguing and characterization of the microbes according to physiological/ molecular properties with more emphasis on halophiles, psychrotrophs and thermophiles is done for exploration for novel bioactives & biocatalysts. Facilities The department has excellent Microprocessor controlled fermentation Microbial enzymes production and their chemoprofiling The prime mandate of the department is to search for microbial strains for novel Fermentation Technology Division, CSIR-IIIM, Jammu 2 Page 2 biocatalysis/ industrially important enzymes for biotransformation. We emphasize more on hydrolases (e.g. lipases, nitrile hydrolyzing enzymes), lyases (c-c bond forming enzymes) and oxidoreductases. Detailed chemoprofiling the enzymatic activity is done for the strains screened positive for specific enzyme activities w.r.t. enantio/ regiospecificity. technology has been successfully demonstrated to Avesthagen Technologies Pvt. Ltd., Bangalore. DHA Microbial enzyme immobilization and biotransformation: Microbial Biofertilizer and biopesticides fermentation processes Enzyme immobilization studies being done to develop the enzyme based cheaper, easy to operate and green processes. Chiral drugs and their intermediates are well known for application in pharmaceutical industry, therefore, we focus on resolution of important drugs or their intermediates using free and immobilized enzymes. We have developed microbial strains of Rhizobium, Azatobacter, Azospirillum and further cultivated under certain specifically defined physico-chemical conditions in 500L fermentor. The fermentation product can be used for nitrogen fixation to increase crop yields. Similarly technology on production of biocontrol agents by submerged and solid state fermentation (SSF) has been transferred to various Indian industries. A strain of Trichoderma viride has been developed which profusely sporulate under submerged fermentation conditions at certain specifically defined physicochemical conditions. The process has been scaled up to 500L scale. Scale up of fermentation processes for stereospecific enzymes production Large scale production of enzymes such as glucose oxidase, glucose dehydrogenases, lipases, esterases, nitrilase, glucosidases, cellulases is being done. Scale-up processes of a few enzymes have been demonstrated to industries. Microbial fermentation process for the production of DHA (docosahexaenoic acid) Microbial industrial Process for metal gluconates A fermentation process for metal gluconates has been developed for production at 40KL. The technology has been transferred to industries and is being produced at 1500TPA. Fermentation technology for production of DHA (cis-4, 7,10,13,16,19Docosahexaenoic Acid) has been developed using marine isolate. The Fermentation Technology Division, CSIR-IIIM, Jammu 3 Page 3 A single step fermentation process allows starch hydrolysate to convert directly to gluconates of Calcium, Sodium, and Barium etc. has been developed. The process is highly cost effective, less energy intensive and environmental friendly. The gluconate salts are used in neutraceuticals, human and veterinary pharmaceuticals, food and cosmetic industry. The products like bio potash and bio zinc produced by this process are also being marketed by the company through out the country as an outcome of our technology for crop yield increase and now many more industries are approaching us for this technology package. Technologies transferred to Indian Industries: 1. Microbial conversion of Glucose to 2ketogluconic acid as an intermediate for isovitamin C production at 4000L scale ( M/s NATCO Pharma, Hyderabad) 2. Kinetic resolution of (RS) Naproxen at 25Kg scale using yeast cells (M/s Searle India, Mumbai) 3. Kinetic resolution process for paroxetine drug intermediate (an anti depressant drug) at 1.0Kg scale (M/s Cadila Zydus, Ahmedabad) 4. Kinetic resolution process for separation of R&S isomers of fluoxetine drug intermediate (anti depressant drug) at 500g scale (M/s Cadila Zydus, Ahmedabad) 5. Fermentation process for the production of Biopesticide and biofertilizer (M/s Prathista Industries, Hyderabad) 6. Fermentation process for the production of Metal-D-gluconates (M/s Prathista Industries, Hyderabad) 7. Fermentation process for the production of Docosahexaneoic acid (DHA) by Schizochytrium sp. (M/s Avesthagen Technologies Pvt. Ltd, Bangalore) 8. Metal gluconates fermentation for use in agriculture (M/s Subash Fertilizer, Aurangabad) 9. Mass cultivation of Bacillus sphaericus by fermentation and its Mosquito Larvicide formulation development (M/s Sri Biotech Laboratories India Ltd, Hyderabad) 10. Fermentation process for production of metal-D-gluconates for human, In recognition of this achievement the Institute has been honored by various awards a) CSIR Technology Award 2001, b) Vasvik Award 2002 and c) 64 th All India Industrial Award for best invention at Hyderabad 2004. Fermentation Technology Division, CSIR-IIIM, Jammu 4 Page 4 veterinary and agriculture use (M/s Sri Biotech Laboratories India Ltd, Hyderabad) 11. A process for protein hydrolysate production (M/s Glow Biotech, Aligarh) 12. Fermentation process for the production of Metal-D-gluconates (M/s Sowbhagya Biotech, Hyderabad) People S/NO Name Expertise E-mail 1. Rajinder Parshad Microbial fermentation technology scale up & down rparshad@iiim.ac.in stream processing, Enzymology, Biotransformation, Enzyme immobilization and bioprocesses development especially resolution of racemic drugs 2. Asha Chaubey Microbial Enzymes, bioactives, endophytes, Enzymes achaubey@iiim.ac.in immobilization, biotransformation and biosensors 3. Vikash Babu Enzyme Technology, Biotransformation 4. R.K. Khajuria Microbiology, bioactives 5. Urmila Jamwal Microbiology, enzymes, bioactives 6. Chandji Raina Microbial Fermentation, endophytes, bioactives biofertilizer & 5 biocontrol process Fermentation Technology Division, CSIR-IIIM, Jammu vikash@iiim.ac.in agent, rkkhajuria@iiim.ac.in ujamwal@iiim.ac.in development, craina@iiim.ac.in Page 5