發(fā)酵工藝：下游加工過程（英文版）

DownstreamProcessing2Downstreamprocessing,whatandwhyDownstreamprocessingisanytreatmentofculturebrothafterfermentationtoconcentrateandpurifyproducts.SeparationProcesses

ThechallengeLowproductconcentrationsLargenumberofimpuritiesThermolabilebioproductsAnidealbioseparationprocessshouldcombinehighthroughputwithhighselectivity,andshouldensurestabilityofproduct.

HappygrowingDrugproducingFermentationKillthemicrobesSmashthemicrobesRemovecells/debrisConcentrateandPurifytheproductFormulateproductDownstreamProcessingMicrobesGeneticmodificationMarketNutrientsOxygenBiologicalproductsProductNatureofbioseparationrequiredAlcoholicbeverages:Beer,wine,spiritsClarification,distillationOrganicacids:Aceticacid,citricacidPrecipitation,filtration,adsorptionVitamins:VitaminC,vitaminB12Precipitation,filtration,adsorptionAminoacids:

Lysine,glycine,Precipitation,filtration,adsorptionAntibiotics:

PenicillinsPrecipitation,filtration,adsorptionEnzyme,PolysaccharidesFiltration,precipitation,centrifugation,adsorption,chromatographyDistillationSeparatingcomponentswithdifferentvolatilities.Suchasorganicsolvents,volatileflavorsandaromas.DistillationStagesinDownstreamProcessing

Removalofinsoluble'sProductIsolation

ProductPurification

ProductPolishing

Cellremoval(filtration,centrifugation)2.Primaryisolation(adsorption,precipitation)RemovingcomponentswithpropertiessignificantlydifferentfromthoseoftheproductsLargevolume,relativelynonselective3.Purification(chromatography,ultrafiltration)RemovingcomponentswithpropertiessimilartothoseoftheproductsHighlyselective4.

Productpreparation(crystallization,drying)Removalofinsoluble's

Captureoftheproductasasoluteinaparticulate-freeliquidExampleSeparationofcells,celldebrisorotherparticulatematterfromfermentationbrothcontaininganantibiotic.TypicalOperationsFiltrationAmechanicaloperationusedfortheseparationofsolidsfromfluids.16TypeoffiltrationunitPlateandframefilterRotary-drumvacuumfilterCentrifugation

UseofthecentrifugalforcefortheseparationofmixturesMore-densecomponentsmigrateawayfromtheaxisandless-densecomponentsmigratetowardstheaxisofthecentrifugeCentrifuges

ttDecantercentrifugeProductIsolationReducingthevolumeofmaterialtobehandledandconcentratingtheproduct.Precipitation

Formationofasolidinasolutionduringachemicalreaction.Solidformediscalledtheprecipitate

andtheliquidremainingabovethesolidiscalledthesupernatant.1.IsoelectricPrecipitation

GA+GA±GA–GA=pH23.227.0>12pI2.Organicsolventprecipitation

Byaddinganorganicsolventtoanaqueousfermentationbroth,thedielectricconstantwilldecreasecausingthesolubilitytodecrease.ExampleXanthangumisrecoveredfromanaqueousfermentedbrothcontainingthegumbyaddingtothebrothorganicsolvent.3.InsolublesaltprecipitationUsuallyusedinextractionofaminoacidandorganicacid.

e.g.CitricacidextractionandpurificationprocessHeating(destroythemicroorganisms)Neutralizition(formingcalciumcitrate)

Acidifying(liberatethecitricacidfromitssalt)Disadvantageshighchemicalcostrelativelycomplextechnology29IonExchangeResinsResinsOrganicorinorganicpolymerusedtoexchangecations(positiveions)

oranions(negativeions)

fromasolutionphaseGeneralStructurePolymerbackbonenotinvolvedinbondingFunctionalgroupforcomplexinganionorcationOrganicResinGroupsLinkagegroupCationexchangeChlorideAnionexchangee.g.

PurificationofLacticAcidfromFermentationBrothsbyIon-ExchangeResins

First,astrongcationresinwasusedtoreducethebrothpHandremovethecationspresentinthesolution;Thentheacidifiedbrothwaspurifiedbyananionexchanger.MembraneSeparation

Function:clarificationandsterilizationAdvantagesNophasechangeEnergyefficientAhigherqualityproductEnvironmentallyfriendlyEasytoscale-upLimitationsLong-termreliabilitynotprovenExcessivepretreatmentConcentrationpolarizationandmembranefoulingReplacementofmembranesMembraneFractionTechnologiesUltrafiltration(2000-50,000MW)Nanofiltration(200-700MW)Microfiltration(100,000MW)ReverseOsmosis(<200MW)WaterSaltsLactoseProteinMicrobes+fatSemi-permeableMembraneWineFiltration–Why?

FiltrationObjectives/PurposesIncludeRemoveinsolublecontaminantsImproveclarity,brightnessExtendshelflife

ElectrodialysisProductPolishing

Finalprocessingstepswhichendwithpackagingoftheproductinaformthatisstable,easilytransportableandconvenientCrystallization,concentrationanddryingaretypicalunitoperationsCrystallizationFormationofacrystallinephasefromaparentphase,e.g.solutionOneoftheoldestandmostimportantunitoperations,e.g.extractingsaltcrystalsfromseawaterDefinitionofCrystalAsubstanceinwhichtheconstituentatoms,molecules,orionsarepackedinaregularlyordered,repeatingthree-dimensionalpattern.ThedistinctionbetweenacrystalandanamorphoussolidisthatbetweenorderanddisorderoverlargedistancesCrystallizationProcessLiquidMixtureGenerationofSupersaturation:DrivingforceNucleation:BirthofSolidPhaseCrystalGrowthFinalProductSupersaturationreferstoastateinwhichtheliquid(solvent)containsmoredissolvedsolids(solute)thancanordinarilybeaccommodatedatthattemperature.Solubility&SupersolubilityDiagramGenerationofsupersaturationSolventevaporationSolutioncoolingAlteringpHCrystallization

-byevaporationofsaturatedsolutionCrystallization

-bycoolingsaturatedsolutionConcentrationFiltrationCentrifugationReducedpressureconcentrationDryingDryinginvolvesthetransferofheattothewet