年产1万吨青霉素原料药工厂发酵车间的设计

本科毕业论文年产1万吨青霉素原料药工厂发酵车间的设计学院生命科学学院专业制药专业生物方向姓名学号指导教师职称讲师设计提交日期二一一年五月摘要青霉素是高效广谱抗生素，其对革兰氏阳性细菌有很好的抑制作用,青霉素的发酵对人们生活中治疗疾病有很好的疗效。青霉素的工艺设计与研究对青霉素工厂的发展有极其重要的作用。国内外有许多家青霉素工厂，要想自己的工厂在众多工厂中立于不败之地，改良工艺设计和对工厂车间设计是一件最起码的要求，比如说工厂空气的净化，工厂车间的消毒。近年来国内外市场对青霉素的需求呈攀升趋势，所以对于青霉素的供应量也逐渐提高，因此，青霉素工厂的发酵车间设计也就非常重要了。关键词青霉素发酵工艺；车间设计ANNUALWORKSHOPOF10,000TONSOFPENICILLINFERMENTATIONDESIGNOFDRUGFACTORYABSTRACTPENICILLINWASEFFICIENTBROADSPECTRUMANTIBIOTICS,ITSGRAMPOSITIVEBACTERIATOHAVEVERYGOODINHIBITORYEFFECTONPEOPLE,PENICILLINFERMENTATIONTOTREATDISEASEINLIFEHAVEVERYGOODCURATIVEEFFECTTHEREAREMANYPENICILLINFACTORIESATHOMEANDABROADTOTHEIRFACTORIESINMANYFACTORIESINTHEFACTORYINVINCIBLE,PROCESSDESIGNANDIMPROVEMENTOFFACTORYWORKSHOPDESIGNISAMINIMUMREQUIREMENT,FOREXAMPLETHEFACTORYWORKSHOPAIRCLEANINGANDDISINFECTIONTHEMARKETFORPENICILLINISINRISINGTRENDATHOMEANDABROADINRECENTYEARS,SODEMANDFORPENICILLINSUPPLYISALSOGRADUALLYIMPROVED,THEREFORE,PENICILLINFERMENTATIONOFWORKSHOPDESIGNALSOFACTORYISSOIMPORTANTKEYWORDSPENICILLINFERMENTATIONTECHNOLOGYWORKSHOPDESIGN1绪论111产品名称112设计依据113工厂设计原则214青霉素药物治疗对G16949215青霉素药物G6365来G9316的G2010G1287922青霉素发酵工艺G8981G12255321青霉素发酵工艺G8981G12255G17347G13459322G3533G1871G3534的G10317G98693221G3533G1871G3534中G2520G6116G2010G10317G986932221G11911G9316的G17885G633332213G7092G7438G1142842215G9167G2164G2081G13194222G3533G1871G3534G12193G12879G10317G9869423菌G12193生G19283524G1039要设G3803工艺G8981G12255G7706G328253工艺G6523制G2462要G9869531工艺G6523制5311G5445G2721发酵产G10587的因素5312G9213G52426313PHG15526314G9354G16311G86996315消G88316316菌G1009G8999G52426317菌G1009生G19283G17907G52427318菌G1009G5430G5589732工艺G6523制要G98697321G12193G4388G17148量的G6523制7322G3533G1871G3534G6116G2010的G6523制8323发酵G3533G1871的G6523制84工艺计G12651941物G7021G15925G126511042G9921量G15925G1265112421生物G992113422G6617G6304G992113423G8785化G992113424发酵G9921145设G3803G17885G34231451工艺G8981G12255G32821452发酵车间G17753G2173设G380314521原G7021G3800G10714设G380314522G451G17767G17877设G380316523G3533G1871G3534G9793菌设G380316524空气G2399G13565G2462G19512菌设G380318525设G3803G12661G17959G9177G8939与G9793菌19526G7092菌G8712设G38031953发酵G13604206车间G5647G1319G5079G46282261车间G13464G61162262车间G5079G4628原则2363车间G5079G4628G328223G14280G1688623G2454G13783G7003G1049825插图和附表清单G32821青霉素G13479G7512求G7841G8181G3423G32821G32822青霉素发酵工艺G7706G3282错误未定义书签。G159321工艺计G12651G3534G11796G6980据9G32823G2464G7366G7576G6683G2172G12591G13479G751214G32825G2464G17758G5347G12893G11874G743815G32827G10711G11964G7438G13479G7512与工作原G1071415G32828G8145G5347G9163G2524G743816G32829G17842G13505G9793菌工艺G8981G12255G6817作17G159324G7507G10267G7444菌设G3803G2454G6980G1593217G328211G7092菌空气制G3803G8981G12255G328218G328212CIPG9177G8939设G3803G8981G12255G328219G328213G1120G13435G2465G9195G17891制G8712工艺20G159325抗生素发酵G13604G2454G698021G328214发酵G13604G12628G328222A2A0A2A1A3A4A5A611绪论11产品名称青霉素G708BENZYLPENICILLIN/PENICILLING709G2460G15999称G1038青霉素GG451PEILLINGG451G11436G4624西林G451配G4624西林G451青霉素钠G451苄青霉素钠G451青霉素钾G451苄青霉素钾。它的G13479G7512G5347G1038青霉素G2010G4388G13479G7512G10711G7841G8181G3423G1038A7A8A9A10A11A12A13A14A15A16A17A7青霉素是内酰胺内抗生素，作用G7438G10714如下G7081G709通过竞争细菌的粘肽G2524G6116酶，即青霉素G13479G2524蛋白G708PENICILLINBINDINGPROTEINS，PBPG709，抑制细胞壁的粘肽G2524G6116，造G6116细菌细胞壁缺损，大量的G8712G2010涌进细菌G1319内，使细菌肿胀G451破裂G451死亡；G7082G709促发自G9354酶活性，使细菌G9354G16311。细菌具有G10317定的细胞壁G2524G6116需要的G2524G6116酶，即青霉素G13479G2524蛋白G708PENICILLINBINDINGPROTEINS,PBPG709当内酰胺G12879抗菌药物与PBPG13479G2524后，PBP便失去酶的活性，是细胞壁的G2524G6116受到阻碍，最终造G6116细胞G9354G16311G451细菌死亡。PBPG6365G2010G4388量的不同可G2010G1038五G12193每G12193G2460有若干亚G3423，这些PBP存在于细菌细胞的G17148膜中，对细菌细胞壁的G2524G6116起不同的作用。12设计依据学士学位论G7003G708设计G709要求A18A191A20A21A22A23A24A25A26A27A28A29A30A31A32A33A34A5A62药品生产G12661G10714规范医药工业洁净厂房设计规范工业企业设计卫生标准等要求G2462对年产1万吨青霉素原G7021药工厂发酵车间的初步设计。13工厂设计原则1贯彻执行国家的方针政策2正确G3800G10714G2520G12193关系3注意制药工业对厂址G17885G6333的G10317殊要求4充G2010G13783虑环境保护和综G2524利用5节约用地6具G3803G3534本的生产条件14青霉素药物治疗对象青霉素对G9354血性链G10711菌等链G10711菌属，肺炎链G10711菌和不产青霉素酶的葡萄G10711菌具有良好抗菌作用。对肠G10711菌有中等G5242抗菌作用，淋病奈瑟菌G451脑膜炎奈瑟菌G451白喉棒状杆菌G451炭疽G14481G4406杆菌G451G10287G3423G6930G13459菌G451G5577G10676状链杆菌G451G7458G7043G10317菌G451G19069G12483G15758G7071G1319和G7769毒G15758G7071G1319对本品G6947G5875。本品对G8981G5875G2992血杆菌和G11346G7097G2695G21089G10317氏菌G1146具一定抗菌活性，其G1194革兰G19464性需G8699G6122G1872性G2400G8699菌对本品G6947G5875性G5058本品对G7809状G14481G4406杆菌属G451消化链G10711菌G451G2400G8699菌以G2462产G21669G14406素G6323杆菌等具良好抗菌作用，对G14042G5381G6323杆菌的抗菌作用G5058。青霉素通过抑制细菌细胞壁G3247肽G1403链和五肽G1144G17842G7737的G13479G2524G13792阻碍细胞壁G2524G6116G13792发G6393G7444菌作用。对革兰阳性菌有效，G11013于革兰G19464性菌缺G1059五肽G1144G17842G7737G13792青霉素对其作用不大。青霉素是治疗G9354血性链G10711菌G5875G7591，肺炎链G10711菌G5875G7591，不产青霉素酶葡萄G10711菌G5875G7591，炭疽，破G1272G20130G451气性G3363疽等G7809状G14481G4406杆菌G5875G7591，G7769毒G2265G6336G1820G3837性G7769毒，G19069G12483G15758G7071G1319病，G3250G5414G9921，白喉，青霉素与G8700G3534G12970G14539G12879药物G13864G2524用于治疗G14621G13523G14406链G10711菌G5527内膜炎的G20330G17885药物，G17836可以治疗其G1194一些炎G11163G5875G7591G12879病G11163。所以青霉素的药用G1227G1552极大，研究设计其工艺和发酵车间设计对于每G1022青霉素工厂具有很好的G13475G8994效G11422。15青霉素药物按来源的分类青霉素G6365对其生产的方G8873G2010G1038G2334G2524G6116青霉素和G3837G9994青霉素G1016G12193。A35A36A35A37A38A39A40A413G3837G9994青霉素生产可G2010G1038菌G12193发酵和提G2474G12946制G1016G1022步G20600。G311菌G12193发酵G4570产G21656青霉菌G6521G12193到G3278G1319G3533G1871G3534G990，在25G263下G3533G18717G79410G3837，即可G5483青霉菌G4406G4388G3533G1871物。用G7092菌G8712G4570G4406G4388制G6116G5760G9026G9094G6521G12193到G12193G4388G13604内G5062G9793菌的G3533G1871G3534中，通G1849G7092菌空；气G451G6617G6304，在27G263下G3533G187124G79428H，G9994后G4570G12193G4388G3533G1871G9094G6521G12193到发酵G13604G5062G9793菌的G2559有G14531G1069G18252G2081G1319的G3533G1871G3534中，通G1849G7092菌空气，G6617G6304，在27G263下G3533G18717G3837。在发酵过G12255中需G15929G1849G14531G1069G18252G2081G1319G2462G17878量的G3533G1871G3534。G312提G2474G12946制G4570青霉素发酵G9094G1931G2376，过G9400。G9400G9094在PH2G79425的条件下，于G14807G2474G7438内用G18271G18252G981G18243进行多G13435G17882G8981G14807G2474，G5483到G981G18243G14807G2474G9094，G17728G1849PH70G79472的G13543G1926G9094中，G9994后G1889G17728G1849G981G18243中，G4570此G981G18243G14807G2474G9094G13475活性炭G14085G14406，G2164G1849G6116G11428G2070，G13475G1861G8844G14988G20323即可G5483青霉素G钾G11428。青霉素G钠G11428是G4570青霉素G钾G11428通过G12175G4388G1144G6454G7653G14038G708钠G3423G709G13792制G5483本G8437是针对G3837G9994青霉素的发酵G18108G2010设计的。产青霉素的菌G7678G2010G1038G10711状菌和G1009状菌。工业生产中G1039要用的菌G7678是产G21656青霉G708PENICILLIUMCHROSOGENUMG709，G4406G4388有G13523G14406与G21656G14406，菌G14865G5191G3386G6122G11397G16138，G3290G5430。青霉G12331是G2010生G4406G4388链状的，G9157层G3533G1871菌G1009G2010G1038G10711状和G1009状G1016G12193。大G18108G2010发酵是G1009状菌发酵。2青霉素发酵工艺流程21青霉素发酵工艺流程路线它们的发酵工艺G8981G12255有所不同AG1009状菌三G13435发酵工艺G8981G12255G1931冻G12661G70825C，G4406G4388G3533G1871，7G3837G709斜面母瓶G70825C，G4406G4388G3533G1871，7G3837G709大米G4406G4388G70826C，G12193G4388G3533G187156H,115VVMG709一G13435G12193G4388G3533G1871G9094G70827C，G12193G4388G3533G1871，24H,115VVMG709G1120G13435G12193G4388G3533G1871G9094G7082726C,发酵,7G3837,1095VVMG709发酵G9094。BG10711状菌G1120G13435发酵工艺G8981G12255G1931冻G12661G70825C，G4406G4388G3533G1871，68G3837G709亲米G70825C，G4406G4388G3533G1871，810G3837G709生产米G70828C，G4406G4388G3533G1871，5660H,115VVMG709G12193G4388G3533G1871G9094G708262524C，发酵，7G3837，108VVMG709发酵G9094。22培养基的特点221培养基中各成分特点2221碳源的选择A42A431A44A45A46A47A48A49A50A51A52A53A54A55A56A57A58A40A414生产菌能利用多G12193G11911G9316，乳G12970G451蔗G12970G451阿拉伯G12970G451甘露G12970G451淀G12893和G3837G9994油G14038。从G13475G8994核G12651角G5242，生产G6116本中G11911G9316占12以G990，对工艺G5445G2721很大。G12970与6APAG13479G2524G5430G6116G12970G35346APA，G5445G2721青霉素的产量。葡萄G12970G451乳G12970G13479G2524能力强，G13792且随时间延G19283G13792增G2164。发酵初期，利用快效的葡萄G12970进行菌G1009生G19283。当葡萄G12970耗尽后，利用G13543效的乳G12970，使PH稳定，G2010泌青霉素。目G2081采用淀G12893的酶G8712G16311产物，葡萄G12970化G9094G8981G2164，G13792不是G8981G2164葡萄G12970，以降低G6116本。2212氮源的选择玉米浆是玉米淀G12893生产时的副产品，是最好的氮G9316，G2559有G2520G12193G8700G3534G18252G2462其G2081G1319G14531G1069G18252和衍生物。但玉米浆G17148量不稳定，可用花生G12893饼G6122用棉G4388饼G12893代替。2213无机盐G2265G6336硫G451磷G451镁G451钾等。铁有毒，G6523制在30G/ML以下。2214流加控制根据残G9094PHG451尾气中CO2和O2的G2559量，残G12970在06左右，PH开始升高时G2164G12970。G8981G2164硫G18252铵G451G8700G8712G451尿素进行G15929氮，G6523制G8700G3534氮005。2215添加前体不G2164G1403链G2081G1319时，青霉素生产多G12193青霉素G9163G2524物。因此在G2524G6116阶段，G9167G2164G14531G1069G18252G2462其衍生物G2081G1319，G14531G1069酰G8700G451G14531G1069G8700G451G14531G1069酰甘G8700G18252等均可G1038青霉素G1403链的G2081G1319，直G6521掺G1849青霉素G2010G4388中，具有刺激青霉素G2524G6116的作用。但G8999G5242大于019时对细胞和G2524G6116有毒性，G17836能G15999细胞G8699化。需要低G8999G5242G8981G2164G2081G1319，一G8437G2164G1849量低于01，保持供应G17907G10587略大于生物G2524G6116需要。发酵过G12255中采用G15929G7021G2010批G6817作G8873，对葡萄G12970G451铵G451G14531G1069G18252进行G13543慢G8981G2164,维持一定的最G17878G8999G5242。葡萄G12970的G8981G2164，波G2172范围较窄，G8999G5242过低使抗生素G2524G6116G17907G10587减慢G6122停止。过高则导G14280呼吸活性下降，甚至引起自G9354，葡萄G12970G8999G5242调节是根据PHG451G9354G8699量G6122CO2释G6930G10587予以调节。222培养基种类特点发酵工艺中,G6365菌G12193生G19283环境顺序，G3533G1871G3534有AG4406G4388G3533G1871G3534甘油G451葡萄G12970G451蛋白胨。B米G4406G4388G3533G1871G3534优G17148小米G6122大米G3278G1319G3533G1871G3534。C一G13435G12193G4388发酵G13604葡萄G12970G451玉米浆G451G11911G18252钙G451玉米油G451消泡G2070等。DG1120G13435G12193G4388发酵G13604玉米浆G451蛋白G17148等。A35A36A35A37A38A39A40A41523菌种生长产青霉菌的菌G12193在发酵条件下，G9157层G3533G1871，G13475历了7G1022不同时期，每G1022时期有其菌G1319G5430G5589G10317征。在规定时间G2474样，通过显微镜检查G708生产G990习惯称G1038镜检G709这些G5430G5589变化，用于过G12255G6523制。第一期G2010生G4406G4388萌发，G5430G6116G14481G12661，原生G17148未G2010化，具有小泡。第G1120期菌G1009繁殖，原生G17148G1319具有G2992碱性，G12879G14038肪小颗粒。第三期G5430G6116G14038肪G2265涵G1319，累积储藏物，没有空泡，G2992碱性强。第G3247期G14038肪G2265涵G1319G5430G6116小滴并减G4581，中小空泡，原生G17148G1319G2992碱性减G5381，开始产生抗生素。第五期G5430G6116大空泡，有中性G7591G14406大颗粒，菌G1009G6116G7754状，G14038肪G2265涵G1319消失，青霉素产量最高。第G1857期G1998G10628G1022G2047自G9354细胞，细胞内G7092颗粒，G1185G9994G7754状，释G6930G9228G12175G8700，PHG990升。第G983期菌G1009G4448G1852自G9354，G1177有空细胞壁。14期G1038菌G1009生G19283期，3期的菌G1319G17878G4464G1038G12193G4388。45期G1038生产期生产能力最强，通过工艺G6526G7057，延G19283此期，G14731G5483高产。在第G1857期到来之G2081G13479G7475发酵。24主要设备工艺流程框图在工艺G17347G13459和生产方G8873确定之后，物G7021G15925G12651开始之G2081G15932G12046生产工艺过G12255的一G12193定性G3282G13452,G16826G16277G19480G3282。3工艺控制及要点31工艺控制311影响发酵产率的因素G3534G17148G8999G5242在G2010批发酵中，常常因G1038G2081期G3534G17148量G8999G5242过高，对生物G2524G6116酶系产生阻G17955G708G6122抑制G709G6122对菌G1009生G19283产生抑制G708如葡萄G12970和G19077的阻G17955G6122抑制,G14531G1069G18252的生G19283抑制G709,G13792后期G3534G17148G8999G5242低G19492制了菌G1009生G19283和产物G2524G6116,G1038了G18003G1825这一G10628G16949,在青霉素发酵中通常采用G15929G7021G2010批G6817作G8873,即对G4493G7143产生阻G17955G451抑制和G19492制作用的G3534G17148进行G13543慢G8981G2164以维持一定的最G17878G8999G5242。这G18336G5529G20047G10317G2047注意的是葡萄G12970的G8981G2164,因G1038即使是G17241G1998最G17878G8999G5242范围较小的波G2172,G18129G4570引起G1017重的阻G17955G6122G19492制,使生物G2524G6116G17907G5242减慢G6122停止。目G2081,G12970G8999A42A431A44A45A46A47A48A49A50A51A52A53A54A55A56A57A58A40A416G5242的检G8991G4590G19602在G13459进行,G6937葡萄G12970的G8981G2164不是依据G12970G8999G5242G6523制,G13792是间G6521根据PHG1552G451G9354G8699G6122C02释G6930G10587予以调节。312温度青霉素发酵的最G17878G9213G5242随所用菌G7678的不同可能G12257有G5058G2047,但一G14336G16760G1038应在25C左右。G9213G5242过高G4570G7138显降低发酵产G10587,同时增G2164葡萄G12970的维持消耗,降低葡萄G12970至青霉素的G17728化G10587。对菌G1009生G19283和青霉素G2524G6116来说,最G17878G9213G5242不是一样的,一G14336G2081G13785略高于后G13785,G6937有的发酵过G12255在菌G1009生G19283阶段采用较高的G9213G5242，以G13565G11713生G19283时间,到G17810生产阶段后便G17878当降低G9213G5242,以利于青霉素的G2524G6116。313PH值青霉素发酵的最G17878PHG1552一G14336G16760G1038在65左右,有时也可以略高G6122略低一些,但应尽量G18003G1825PHG1552G17241过70,因G1038青霉素在碱性条件下不稳定,G4493G7143G2164G17907其G8712G16311。在G13543G1926能力较G5381的G3533G1871G3534中,PHG1552的变化是葡萄G12970G8981G2164G17907G5242高低的G2465G7156。过高的G8981G2164G17907G10587造G6116G18252性中间产物的积累使PHG1552降低过低的G2164G12970G17907G10587不G17287以中和蛋白G17148代G16886产生的G8700G6122其G1194生G10714碱性物G17148代G16886产生的碱性化G2524物G13792引起PHG1552G990升。314溶解氧对于好G8699的青霉素发酵来说,G9354G8699G8999G5242是G5445G2721发酵过G12255的一G1022重要因素。当G9354G8699G8999G5242降30G20293和G5242以下时,青霉素产G10587G5625G2107下降,低于10G20293和G5242时,则造G6116不可G17882的损G4487。G9354G8699G8999G5242过高,说G7138菌G1009生G19283不良G6122G2164G12970G10587过低,造G6116呼吸强G5242下降,同样G5445G2721生产能力的发G6393。G9354G8699G8999G5242是G8699G1268G17894和G8699消耗的一G1022G2172G5589G5191G15925G9869,G13792G8699消耗与G11911能G9316消耗G6116正比,G6937G9354G8699G8999G5242也可作G1038葡萄G12970G8981G2164G6523制的一G1022G2454G13783G6363标。315消沫发酵过G12255泡G8831较多，需要G2164G1849消G8831G2070，G3837G9994油G14038如玉米油，化学消G8831G2070如泡G6944。G4581量多G8437，不G17878在G2081期多G2164G1849，G5445G2721呼吸代G16886。316菌丝浓度发酵过G12255中G5529G20047G6523制菌G1009G8999G5242不G17241过G1032G11040菌G1319G8999G5242,从G13792使G8699G1268G17894G17907G10587与G8699消耗G17907G10587在G7588一G9354G8699G8712G5191G990G17810到G5191G15925。青霉素发酵的G1032G11040菌G1319G8999G5242A59A60A59A61A62A63A64A657随菌G7678的呼吸强G5242G2474G1927于维持因G6980的大小,维持因G6980G17246大,呼吸强G5242G17246高G451发酵通气与G6617G6304能力G2462发酵的G8981变学性G17148G13792G5334。呼吸强G5242低的菌G7678降低发酵中G8699的消耗G17907G10587，G13792通气与G6617G6304能力强的发酵G13604G2462G21667G5242低的发酵G9094使发酵中的G1268G8699G17907G10587G990升,从G13792提高G1032G11040菌G1319G8999G5242。317菌丝生长速度用G5670化G3132进行的发酵G16809G20576G16789G7138，在葡萄G12970G19492制生G19283的条件下，青霉素比生产G17907G10587与产生菌菌G1009的比生G19283G17907G10587之间呈G10628一定的关系。当比生G19283G17907G10587低于0015H1H的时G1517，比生产G17907G10587与比生G19283G17907G10587G6116正比,当比生G19283G17907G10587高于0015H1H时,比生产G17907G10587与比生G19283G17907G10587G7092关D因此,要在发酵过G12255中G17810到并维持最大比生产G17907G10587,G5529G20047使比生G19283G17907G10587不低0015H1H。这一比生G19283G17907G10587称G1038G1032G11040比生G19283G17907G10587。对于G2010批G15929G7021发酵的生产阶段来说,维持0015H的G1032G11040比生G19283G17907G10587意G2631G11540每46H就要使菌G1009G8999G5242G6122发酵G9094G1319积G2164G1505,这在G4466G19481工业生产中是很G19602G4466G10628的。G1119G4466G990,青霉素工业发酵生产阶段G6523制的比生G19283G17907G10587要比这一G10714论G1032G11040G1552低G5483多,G2376G1185G9994能G17810到很高的比生产G17907G10587。这是G11013于工业G990采用的G15929G7021G2010批发酵过G12255不G7041有G18108G2010菌G1009自G9354,G6281消了一G18108G2010生G19283,G6937G15441G9994G15932G16278比生G19283G17907G10587低,但G11507比生G19283G17907G10587G2376要高一些。318菌丝形态在G19283期的菌G7678改良中,青霉素产生菌在G8797没G3533G1871中G2010化G1038G1039要呈G1009状生G19283和G13479G10711生G19283G1016G12193G5430G5589。G2081G13785G11013于所有菌G1009G1319G18129能充G2010和发酵G9094中的G3534G17148G2462G8699G6521G16314,G6937一G14336比生产G17907G10587较高；后G13785则G11013于发酵G9094G21667G5242显G14891降低,使气G9094G1016G11468间G8699的G1268G17894G17907G10587大大提高,从G13792G1813许G7368多的菌G1009生G19283即G1032G11040菌G1319G8999G5242较高,发酵G13604G1319积产G10587甚至高于G2081G13785。在G1009状菌发酵中,G6523制菌G1009G5430G5589使其保持G17878当的G2010G6915和G19283G5242,并G18003G1825G13479G10711,是G14731G5483高产的关G19202要素之一。G13792在G10711状菌发酵中,使菌G1009G10711保持G17878当大小和G7506G13051,并尽量减G4581G9228G12175菌G1009的G2559量,也是充G2010发G6393其生产能力的关G19202素之一。这G12193G5430G5589的G6523制与G12970和氮G9316的G8981G2164状G1929G2462G17907G10587G451G6617G6304的G2110G2011强G5242G2462比生G19283G17907G10587G4506G2011G11468关。32工艺控制要点321种子质量的控制A66A671A68A69A70A71A72A73A74A75A76A77A78A79A80A81A82A64A658G1009状菌的生产G12193G4388是G11013保藏在低G9213的G1931冻G4445G10963G12661G13475甘油G451葡萄G12970G451蛋白胨斜面G12239G7905到小米G3278G1319G990，25CG3533G18717G3837,G11507空干G10169并以这G12193G5430G5347保存G3803用。生产时它G6365一定的G6521G12193量G12239G12193到G2559有葡萄G12970G451玉米浆G451尿素G1038G1039的G12193G4388G13604内,26CG3533G187156H左右,菌G1009G8999G5242G1781068,菌G1009G5430G5589正常,G63651015的G6521G12193量G12239人G2559有花生饼G12893G451葡萄G12970G1038G1039的G1120G13435G12193G4388G13604内,27CG3533G187124H,菌G1009G1319积1012,G5430G5589正常,效G1227在700D/ML左右便可作G1038发酵G12193G4388。G10711状菌的生产G12193G4388是G11013G1931冻G12661G4388G4406G4388G13475G9163有0510玉米浆的三角瓶G3533G1871原始亲米G4406G4388,G9994后G1889G12239人G13611氏瓶G3533G1871生产大米G6277G4388G2460称生产米,亲米和生产米均G103825CG19757G13634G3533G1871,需G13475常G16278G4531生G19283发G13958G5785G1929在G3533G1871到34G3837,大米G15932面G19283G1998G7138显小G19610G14865时要G6403G6683均G2260,使菌G1009在大米G15932面能均G2260生G19283,G546510G3837左右G5430G6116G13523G14406G4406G4388即可G6922G14731。亲米G6116G10099G6521人生产米后也要G13475过激G9884G6403G14645G6177可G6930G13634G5670G9213G3533G1871,生产米的G4406G4388量要求每粒米300万G2494以G990。亲米G451生产米G4388G4406G4388G18129需保存在5CG1924G12677内。工艺要求G4570G7044G21104的生产米G6363G6922G14731后的G4406瓶在10G3837以内使用G6521人G2559有花生饼G12893G451玉米G13998G14481G12893G451葡萄G12970G451G20296G12970G1038G1039的G12193G4388G13604内,28CG3533G18715060H当PHG1552G110136065下降至5550,菌G1009呈G14750花G3254状,G5191均直G5464在100130M,每G8639升的G10711G6980G10386万8万G2494,G8797降G10587在85以G990,即可根据发酵G13604G10711G6980G6523制在800011000G2494/ML范围的要求,计G12651G12239G12193G1319积,G9994后G6521G1849发酵G13604,多G1325的G12193G4388G9094弃去。G10711状菌以G7044G21104G4406G4388G1038佳,其生产G8712G5191优于G11507空干G10169的G4406G4388，能使青霉素发酵单位的G13604批G5058G5334减G4581。322培养基成分的控制AG11911G9316产G21656青霉菌可利用的G11911G9316有乳G12970G451蕉G12970G451葡萄G12970等。目G2081生产G990普遍采用的是淀G12893G8712G16311G12970G451G12970化G9094DEG155250以G990进行G8981G2164。B氮G9316氮G9316常G17885用玉米浆G451G12946制棉籽饼G12893G451麸皮，并G15929G2164G7092G7438氮G9316G708硫G18252G8700G451G8700G8712G6122尿素G709。CG2081G1319生物G2524G6116G2559有苄G3534G3534G3254的青霉素G,需在发酵G9094中G2164人G2081G1319。G2081G1319可用G14531G1069G18252G451G14531G1069酰胺,一G8437G2164G1849量不大于01,并采用多G8437G2164G1849,以防止G2081G1319对青霉素的毒G4487。DG7092G7438G11428G2164G1849的G7092G7438G11428G2265G6336硫G451磷G451钙G451镁G451钾等,且用量要G17878G5242。另外,G11013于铁G12175G4388对青霉菌有毒G4487作用,G5529G20047G1017格G6523制铁G12175G4388的G8999G5242,一G14336G6523制在30G/ML323发酵培养的控制A83A84A83A85A86A87A88A8991G2164G12970G6523制G2164G12970量的G6523制是根据残G12970量G2462发酵过G12255中的PHG1552确定,最好是根据排气中CO2量G2462O2量来G6523制,一G14336在残G12970降至06左右，PHG1552G990升时开始G2164G12970。2G15929氮G2462G2164G2081G1319G15929氮是G6363G2164硫G18252铵G451G8700G8712G6122尿素,使发酵G9094G8700氮G6523制在01005,G15929G2081G1319以使发酵G9094中残存G14531G1069酰胺G8999G5242G1038005008。3PHG1552G6523制对PHG1552的要求视不同菌G12193G13792G5334,一G14336G1038PH6468,可以G15929G2164葡萄G12970来G6523制。目G2081一G14336采用G2164G18252G6122G2164碱G6523制PHG15524G9213G5242G6523制G2081期25C26C,后期23C,以减G4581后期发酵G9094中青霉素的降G16311破G3363。5G9354G16311G8699的G6523制一G14336要求发酵中G9354G16311G8699量不低于G20293和G9354G16311G8699的30。通G20130比一G14336G1038108L/LMIN,G6617G6304G17728G17907在发酵G2520阶段应根据需要G13792调整。6泡G8831的G6523制在发酵过G12255中产生大量泡G8831,可以用G3837G9994油G14038,如豆油G451玉米油等G6122用化学G2524G6116消泡G2070“泡G6944“来消泡,应当G6523制其用量并要G4581量多G8437G2164G1849,尤其在发酵G2081期不G4464多用,否则会G5445G2721菌G1319的呼吸代G168867发酵G9094G17148量G6523制生产G990G6365规定时间从发酵G13604中G2474样,用显微镜G16278G4531菌G1009G5430G558