Podcast
Questions and Answers
What was Sir Alexander Fleming's primary contribution to the discovery of penicillin?
What was Sir Alexander Fleming's primary contribution to the discovery of penicillin?
- Creating a large-scale production process
- Identifying penicillin's antibiotic properties
- Isolating penicillin from mold (correct)
- Developing a synthetic version of penicillin
Which scientists played a significant role in the industrial scale-up of penicillin manufacture?
Which scientists played a significant role in the industrial scale-up of penicillin manufacture?
- Florey and Chain (correct)
- Huxley and Crick
- Fleming and Watson
- Chain and Watson
What best describes the term 'downstream processing' in the context of fermentation?
What best describes the term 'downstream processing' in the context of fermentation?
- The collection of cells and purification methods applied after fermentation (correct)
- The growth techniques used before fermentation starts
- The genetic engineering of fermentation organisms
- The initial fermentation process for growing the cells
What does 'upstream fermentation' encompass in the context of antibiotic production?
What does 'upstream fermentation' encompass in the context of antibiotic production?
What is one example of another discovery made by Sir Alexander Fleming?
What is one example of another discovery made by Sir Alexander Fleming?
What is the main advantage of using the fed batch method in penicillin production?
What is the main advantage of using the fed batch method in penicillin production?
Which ingredient is commonly added to the penicillin production media to provide carbohydrates?
Which ingredient is commonly added to the penicillin production media to provide carbohydrates?
What significant problem arises during the batch culture phase of penicillin production?
What significant problem arises during the batch culture phase of penicillin production?
What technique has been used to grow unculturable microbes for antibiotic discovery?
What technique has been used to grow unculturable microbes for antibiotic discovery?
Which method is used to filter out solids during the penicillin purification process?
Which method is used to filter out solids during the penicillin purification process?
Penicillin G can be chemically treated to create which compound that is useful for further modification?
Penicillin G can be chemically treated to create which compound that is useful for further modification?
What is the role of corn steep liquor in penicillin production media?
What is the role of corn steep liquor in penicillin production media?
Why is there a need for isolation and screening in strain selection for antibiotic discovery?
Why is there a need for isolation and screening in strain selection for antibiotic discovery?
What complication does scaling up the penicillin production process involve?
What complication does scaling up the penicillin production process involve?
Which of the following best describes the effect of higher penicillin concentrations during production?
Which of the following best describes the effect of higher penicillin concentrations during production?
What was the significance of the discovery of Penicillium notatum in 1928?
What was the significance of the discovery of Penicillium notatum in 1928?
How does penicillin disrupt bacterial growth?
How does penicillin disrupt bacterial growth?
Which granted Howard Florey and Ernst Chain a Nobel Prize?
Which granted Howard Florey and Ernst Chain a Nobel Prize?
What kind of ring structure is crucial to the effectiveness of penicillin?
What kind of ring structure is crucial to the effectiveness of penicillin?
Why must strains of penicillium be carefully selected for industrial production?
Why must strains of penicillium be carefully selected for industrial production?
What is the purpose of creating mutant spores in the industrial production of penicillin?
What is the purpose of creating mutant spores in the industrial production of penicillin?
In which phase is penicillin produced during fungal growth?
In which phase is penicillin produced during fungal growth?
How does penicillin affect gram-positive bacteria specifically?
How does penicillin affect gram-positive bacteria specifically?
What key process follows the addition of penicillin precursor phenylacetic acid in industrial production?
What key process follows the addition of penicillin precursor phenylacetic acid in industrial production?
What role do beta-lactamases play in relation to penicillin?
What role do beta-lactamases play in relation to penicillin?
What process is used to crystallize penicillin during its production?
What process is used to crystallize penicillin during its production?
Which of the following statements about penicillin is false?
Which of the following statements about penicillin is false?
What is typically done with leftover solvents after penicillin production?
What is typically done with leftover solvents after penicillin production?
What undesirable effect did the lack of sufficient penicillin have on the first human trials?
What undesirable effect did the lack of sufficient penicillin have on the first human trials?
Flashcards
Fermentation
Fermentation
The process of growing cells to produce a desired product, such as antibiotics.
Upstream Fermentation
Upstream Fermentation
All the steps involved in preparing and carrying out the fermentation process, including preparing the culture media and growing the cells.
Downstream Processing
Downstream Processing
All the steps involved in processing the fermented broth after it has been produced, such as separating the cells from the broth, purifying the desired product, and packaging it.
Metabolism
Metabolism
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Purification
Purification
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Strain Selection
Strain Selection
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Isolation and Screening
Isolation and Screening
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Strain Improvement
Strain Improvement
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Batch Culture
Batch Culture
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Fed Batch Culture
Fed Batch Culture
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Scale Up
Scale Up
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Batch Fermentation
Batch Fermentation
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Biosynthetic Penicillin
Biosynthetic Penicillin
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Penicillin G
Penicillin G
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What is penicillin?
What is penicillin?
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What is the beta-lactam ring?
What is the beta-lactam ring?
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What is the R-group in penicillin?
What is the R-group in penicillin?
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What is 6-Aminopenicillanic acid?
What is 6-Aminopenicillanic acid?
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How does penicillin work on bacterial cells?
How does penicillin work on bacterial cells?
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What specific process does penicillin interfere with in bacterial cells?
What specific process does penicillin interfere with in bacterial cells?
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Why are specific strains of Penicillium mold chosen for industrial production?
Why are specific strains of Penicillium mold chosen for industrial production?
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How are mutant spores of Penicillium created for industrial production?
How are mutant spores of Penicillium created for industrial production?
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What are the key stages for industrial production of penicillin?
What are the key stages for industrial production of penicillin?
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How is penicillin purified after production?
How is penicillin purified after production?
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How is penicillin crystallized?
How is penicillin crystallized?
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What are secondary metabolites?
What are secondary metabolites?
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Why does Penicillium Chrysogenum produce antibiotics?
Why does Penicillium Chrysogenum produce antibiotics?
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What is the relationship between penicillin production and fungal growth?
What is the relationship between penicillin production and fungal growth?
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What is the significance of penicillin?
What is the significance of penicillin?
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Study Notes
Early Discovery of Penicillin
- Alexander Fleming discovered penicillin in 1928 when a Penicillium fungus accidentally contaminated a bacterial culture plate, killing the bacteria.
- He also discovered lysozyme, an enzyme found in bodily secretions that protects against pathogens.
- Fleming published his findings in 1929, but this didn't initially lead to wider interest or action.
Florey and Chain's Role in Industrialization
- Howard Florey and Ernst Chain purified penicillin in 1939, leading to subsequent successful animal trials and eventually human treatments.
- They recognized the need for large-scale production and initiated efforts in the US due to post-war needs in England.
- Their work culminated in winning the Nobel Prize in 1945.
Penicillin's Structure and Action
- Penicillin contains a beta-lactam ring, which is structurally unstable due to the amide bond.
- The amide bond can be hydrolysed by beta-lactamases produced by bacteria, making some bacteria resistant to penicillin.
- Penicillin interferes with the synthesis of peptidoglycan in bacterial cell walls, targeting gram-positive species.
- The process of cell division is halted as cell walls weaken, leading to bacterial cell lysis.
Large-Scale Fermentation of Penicillin
- Industrial production requires selecting Penicillium strains resistant to hostile conditions during large-scale growth.
- This is achieved through steps including: (1) creating mutant spores using stress-inducing methods; (2) testing new strains for industrial survival abilities in a pilot plant; (3) inoculating small- and large-scale liquid cultures; (4) monitoring nutrient availability during the growth cycles and maximizing penicillin synthesis.
Downstream Processing
- Separating and purifying penicillin are critical steps afterward.
- Mycelium is removed, broth is adjusted to a low pH and penicillin is extracted by a solvent (butyl acetate).
- Penicillin is crystallized and purified using various methods (e.g., chromatography, precipitation).
- Waste solvents are recycled to minimize environmental impact and optimize resource utilization.
Penicillin Industrial Production
- Strain Selection: Isolating and screening fungal strains for optimal antibiotic production, often through mutagenesis or genetic manipulation.
- Scale-Up: Gradually increasing culture sizes (test tubes → flasks → fermenters)
- Fed Batch Fermentation: Manipulating the batch culture to maintain cells in a log phase and increase penicillin production.
- Purification and Crystallization: Penicillin's purification using various process steps: filtration, solvent extraction, crystallization to obtain a potent and highly concentrated product.
Industrial Penicillin Media Composition
- Penicillin production media consists of glucose or lactose, corn steep liquor, starch, ammonium sulfate, and phosphates, each playing a crucial role in fungal growth.
- Choosing the appropriate media and ratio is critical to obtain good yield.
Batch vs. Fed Batch in Fermentation
- Batch fermentation produces penicillin primarily at the end of the fermentation cycle, whereas Fed Batch fermentation maintains longer periods in the log phase (growth), enabling more time for penicillin production.
Other methods of antibiotic discovery
- Traditional antibiotic discovery approaches often yielded few new discoveries recently.
- Researchers now use new culture-independent methods, such as environmental sampling via dialysis tubing, to explore unculturable microbial communities in natural environments and discover new antibiotics.
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Description
Explore the groundbreaking discovery of penicillin by Alexander Fleming in 1928 and the subsequent industrialization efforts by Howard Florey and Ernst Chain. Understand the structure and action of penicillin, including its beta-lactam ring and the challenges posed by bacterial resistance. This quiz covers key historical and scientific advancements in antibiotic development.