北京大学：《微生物学》课程PPT教学课件（英文版）Flowsheet for developing an industrial microbial fermentation process

Flowsheet for developing an industrial microbial fermentation process Strain selection Laboratory process development Pilot Scale up Industrial Scale up Downstream process development Product packaging techniques Other commercial consideration Examples

Flowsheet for developing an industrial microbial fermentation process • Strain selection • Laboratory process development • Pilot Scale up • Industrial Scale up • Downstream process development • Product packaging techniques • Other commercial consideration • Examples

Downstream Process Prehminary treatments Development Ferment Solids Filtration Filter(press filter) Liquid Alternate purification method Extract Drac Adsorption Chemical Solvent columns precipitaton extraction Wast Chromatography Partially purified antibiotic in solution Recrystallization Dryer Purification Animal feed supplement Antibio

Downstream Process Development Chromatography Filter (press filter)

Downstream Process Development Stock culture Flask culture Seed culture Sterile medum Intermediate Antifoam fermentor Continuous centrifuges Feist centration washing °g° Cool storage Production fermentor () Dewatering→+ Compressing Packaging--Cold storageCompressed yeast cakes ing--Extruding→d→ Packaging-- Cool storag Active dry yeast Pasteurizing→ Drum drying→ Grinding→- Packaging→ Dry storage Nutritional dry yeast

Downstream Process Development Continuous centrifuges

Unit Operations in Downstream Separation · Microfilters · Ultrafiltration Size Gel chromatograp Reverse osmosis Diffusivity Dialysis Electrodialysis Ion exchange on exchange Distillation/freeze dr Vapour temperature, pressure · Solvent extraction Solubility Foam and bubble fractionation Surface activity Ultracentrifugation ° Centrifugation Density Liquid cyclones Gravity sedimentation

Unit Operations in Downstream Separation • Microfilters • Ultrafiltration • Gel chromatography • Reverse osmosis • Dialysis • Electrodialysis • Ion exchange • Distillation/freeze dry • Solvent extraction • Foam and bubble fractionation • Ultracentrifugation • Centrifugation • Liquid cyclones • Gravity sedimentation Size Diffusivity Ion exchange Vapour temperature, pressure Solubility Surface activity Density

Processing fermentation broth Fermentation Dilute slurry Centrifugation filtration Sedimentation Clarified liquor Concentrated slur Filtration Dewatering Drying Bright liquor Dry biomass

Processing fermentation broth Fermentation Dilute slurry Centrifugation Filtration Sedimentation Clarified liquor Filtration Bright liquor Concentrated slurry Dewatering Drying Dry Biomass

Centrifugation: Continuous centrifugation N

Centrifugation: Continuous centrifugation

Disc-Centrifuges (1 Solids-retaining Nozzle with pressurized Nozzle with peripheral centrifuge discharge of concentrate nozzles Periodically Periodically solids-ejecting sollds-ejecting centrifuge with centrifuge axial channe Is

Disc-Centrifuges Solids-retaining centrifuge Nozzle with pressurized discharge of concentrate Nozzle with peripheral nozzles Periodically solids-ejecting centrifuge Periodically solids-ejecting centrifuge with axial channels

Product Packaging Techniques Steril Packaging Techniques for Medical Applications and Food preservation Pyrogen Free and steril Packaging for Injection Purpose Freeze Dry Packaging for Foods or Medicines Dewatered Packaging(such as Dry Yeast) Normal Food Packaging(such as Na-glutamate) Salty Packaging Preservation Chemicals Ordinary Packaging

Product Packaging Techniques • Steril Packaging Techniques for Medical Applications and Food Preservation • Pyrogen Free and Steril Packaging for Injection Purpose • Freeze Dry Packaging for Foods or Medicines • Dewatered Packaging (such as Dry Yeast) • Normal Food Packaging (such as Na-glutamate) • Salty Packaging • Preservation Chemicals • Ordinary Packaging

Other Commercial Consideration Strengths and weaknesses of biotechnological processes Strengths eaknesses Reliance on renewable Feedstocks are oxidized and feedstocks unsuitable for many applications Versatility with different Feedstock costs fluctuate feedstocks Sterilization is a major cost Food, feed and drug Product often in dilute aqueous applications solutions Fine chemicals to bulk Product recovery costly chemical applications Equipment costs high Low temperature Reactions slow leading to poor Operation in aqueous media volumetric productivity Several reactions achieved in Complicated reaction conditions a single fermentation step Mainly batch operation High level of automation High cell(catalyst) regeneration Stereospecificity costs Complex molecules High BOD wastes converted and/or produced Benign effluents produced

Other Commercial Consideration Strengths and weaknesses of biotechnological processes • Strengths – Reliance on renewable feedstocks – Versatility with different feedstocks – Food, feed and drug applications – Fine chemicals to bulk chemical applications – Low temperature – Operation in aqueous media – Several reactions achieved in a single fermentation step – High level of automation – Stereospecificity – Complex molecules converted and/or produced – “Benign” effluents produced • Weaknesses – Feedstocks are oxidized and unsuitable for many applications – Feedstock costs fluctuate – Sterilization is a major cost – Product often in dilute aqueous solutions – Product recovery costly – Equipment costs high – Reactions slow leading to poor volumetric productivity – Complicated reaction conditions – Mainly batch operation – High cell (catalyst) regeneration costs – High BOD wastes

Other Commercial Consideration Cost evaluation Outline of total capital investment Fixed capl Direct costs (Land, site development, buildings processing, services Indirect costs (Engineering, construction Contingency, Fees Start-up costs Working capital Inventory, accounts receivable, account payable

Other Commercial Consideration Cost Evaluation • Outline of total capital investment • Fixed capital – Direct costs (Land, site development, buildings, processing, services) – Indirect costs (Engineering, construction, Contingency, Fees) – Start-up costs • Working capital – Inventory, accounts receivable, account payable