青霉素简介（英文ppt）production of penicillin课件

Production of penicillinProduction of penicillin Learning objective:Learning objective: To be able to identify useful products from To be able to identify useful products from microorganismsmicroorganisms To be able to identify the microorganisms To be able to identify the microorganisms used and the main stages in the production used and the main stages in the production of penicillin.of penicillin. To be able to describe how Downstream To be able to describe how Downstream processing is carried out to extract and processing is carried out to extract and purify the end-product of fermentation.purify the end-product of fermentation. Downstream Processing Products in a Products in a fermenterfermenter are impure and are impure and dilute, so need to be purified by downstream dilute, so need to be purified by downstream cessing. This usually involves filtration to separate This usually involves filtration to separate the microbial cells from the liquid medium, the microbial cells from the liquid medium, followed by chemical purification and followed by chemical purification and concentration of the product concentration of the product Downstream processing can account for 50% Downstream processing can account for 50% of the cost of a process.of the cost of a process. Antibiotics are antimicrobial agents Antibiotics are antimicrobial agents produced naturally by other microbes produced naturally by other microbes (usually fungi or bacteria).(usually fungi or bacteria). The first antibiotic was discovered in The first antibiotic was discovered in 1896 by Ernest Duchesne and 1896 by Ernest Duchesne and “rediscovered“ “rediscovered“ byAlexanderbyAlexander FlemmingFlemming in 1928 from the filamentous fungus in 1928 from the filamentous fungus PeniciliumPenicilium notatunotatumm. . The antibiotic substance, named The antibiotic substance, named penicillin, was not purified until the penicillin, was not purified until the 1940s (by 1940s (by FloreyFlorey and Chain), just in and Chain), just in time to be used at the end of the time to be used at the end of the second world war.second world war. Penicillin was the first important Penicillin was the first important commercial product produced by an commercial product produced by an aerobic, aerobic, submerged submerged fermentationfermentation When penicillin was first made at the When penicillin was first made at the end of the second world war using the end of the second world war using the fungus fungus PeniciliumPenicilium notatumnotatum, the , the process made 1 mg dmprocess made 1 mg dm-3 -3 . . Today, using a different species (Today, using a different species (P. P. chrysogenumchrysogenum) and a better extraction ) and a better extraction procedures the yield is 50 g dmprocedures the yield is 50 g dm-3 -3 . . There is a constant search to improve There is a constant search to improve the yield. the yield. Antibiotics can be selectively toxic by Antibiotics can be selectively toxic by targeting such features as the bacterial targeting such features as the bacterial cell wall, 70S cell wall, 70S ribosomesribosomes, and enzymes , and enzymes that are specific to bacteria. that are specific to bacteria. In this way the human eukaryotic cells In this way the human eukaryotic cells are unaffected. are unaffected. For example:For example: penicillin, penicillin, ampicillinampicillin, , amoxycillinamoxycillin, , methicillinmethicillin Inhibits enzymes involved in synthesis Inhibits enzymes involved in synthesis of of peptidoglycanpeptidoglycan for bacterial cell wall, for bacterial cell wall, causing cell causing cell lysislysis. . BacteriocidalBacteriocidal Narrow spectrum- little effect on Gram Narrow spectrum- little effect on Gram negative cells.negative cells. Other antibiotics MO may affect:Other antibiotics MO may affect: Cell membraneCell membrane DNA replicationDNA replication TranscriptionTranscription TranslationTranslation Antibiotic productionAntibiotic production There are over 10 000 different antibiotics There are over 10 000 different antibiotics known, but only about 200 in commercialknown, but only about 200 in commercial use, since most new antibiotics are no better use, since most new antibiotics are no better than existing ones. than existing ones. There is a constant search for new There is a constant search for new antibiotics. Antibiotics are the most-antibiotics. Antibiotics are the most- prescribed drugs and are big business. prescribed drugs and are big business. Finding a new antibiotic and getting it on to Finding a new antibiotic and getting it on to the market is a very long process and can the market is a very long process and can take 15 years.take 15 years. Antibiotic Production MethodsAntibiotic Production Methods Antibiotics are produced on an industrial scale Antibiotics are produced on an industrial scale using a variety of fungi and bacteria. using a variety of fungi and bacteria. Penicillin is produced by the fungus Penicillin is produced by the fungus PenicilliumPenicillium chrysogenumchrysogenum which requires lactose, other which requires lactose, other sugars, and a source of nitrogen (in this case a sugars, and a source of nitrogen (in this case a yeast extract) in the medium to grow well.yeast extract) in the medium to grow well. Like all antibiotics, penicillin is a secondary Like all antibiotics, penicillin is a secondary metabolite, so is only produced in the metabolite, so is only produced in the stationary phase. stationary phase. What sort of What sort of fermenterfermenter does it require? does it require? It requires a batch It requires a batch fermenterfermenter, and a fed batch , and a fed batch process is normally used to prolong the process is normally used to prolong the stationary period and so increase production.stationary period and so increase production. Downstream processing is relatively Downstream processing is relatively easy since penicillin is secreted into easy since penicillin is secreted into the medium (to kill other cells), so there the medium (to kill other cells), so there is no need to break open the fungal is no need to break open the fungal cells.cells. However, the product needs to be very However, the product needs to be very pure, since it being used as a pure, since it being used as a therapeutic medical drug, so it is therapeutic medical drug, so it is dissolved and then precipitated as a dissolved and then precipitated as a potassium salt to separate it from other potassium salt to separate it from other substances in the medium. substances in the medium. The resulting penicillin (called penicillin The resulting penicillin (called penicillin G) can be chemically and G) can be chemically and enzymaticallyenzymatically modified to make a variety of modified to make a variety of penicillinspenicillins with slightly different properties. with slightly different properties. These semi-synthetic These semi-synthetic penicillinspenicillins include penicillin V, penicillin O, include penicillin V, penicillin O, ampicillinampicillin and and amoxycillinamoxycillin. . What is the Carbon source?What is the Carbon source? What is the nitrogen source?What is the nitrogen source? What is the energy source?What is the energy source? Is the fermentation aerobic or anaerobic?Is the fermentation aerobic or anaerobic? What is the optimum temperature?What is the optimum temperature? Is penicillin a primary or secondary metabolite?Is penicillin a primary or secondary metabolite? What volume What volume fermenterfermenter is used? is used? Why isnt a larger Why isnt a larger fermenterfermenter used? used? When is penicillin produced?When is penicillin produced? How long can it be produced for?How long can it be produced for? What was the first fungus known to produce penicillin?What was the first fungus known to produce penicillin? What species produces about 60mg/dm3 of penicillin?What species produces about 60mg/dm3 of penicillin? How did scientists improve the yield still further?How did scientists improve the yield still further? What is the substrate?What is the substrate? Why is batch culture used?Why is batch culture used? What are the processes involved in down-stream processing?What are the processes involved in down-stream processing? a)a) b)b) c)c) Why cant penicillin be taken orally?Why cant penicillin be taken orally? Name the form of penicillin which can be taken orally.Name the form of penicillin which can be taken orally. How does Penicillin kill bacteria?How does Penicillin kill bacteria? Why are Gram negative bacteria not killed by penicillin?Why are Gram