Discovery and Impact of Penicillin

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Questions and Answers

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?

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?

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?

The fermentation and growth of the cells prior to product recovery Signup and view all the answers

What is one example of another discovery made by Sir Alexander Fleming?

Lysozyme Signup and view all the answers

What is the main advantage of using the fed batch method in penicillin production?

It allows cells to produce penicillin over a longer time. Signup and view all the answers

Which ingredient is commonly added to the penicillin production media to provide carbohydrates?

Starch Signup and view all the answers

What significant problem arises during the batch culture phase of penicillin production?

Penicillin is only produced at the end of fermentation. Signup and view all the answers

What technique has been used to grow unculturable microbes for antibiotic discovery?

Embedding samples in dialysis bags. Signup and view all the answers

Which method is used to filter out solids during the penicillin purification process?

Filtration Signup and view all the answers

Penicillin G can be chemically treated to create which compound that is useful for further modification?

6-Aminopenicillanic acid Signup and view all the answers

What is the role of corn steep liquor in penicillin production media?

Helps to increase penicillin production. Signup and view all the answers

Why is there a need for isolation and screening in strain selection for antibiotic discovery?

To identify new and effective antibiotic-producing strains. Signup and view all the answers

What complication does scaling up the penicillin production process involve?

Inoculating small volumes into much larger ones directly. Signup and view all the answers

Which of the following best describes the effect of higher penicillin concentrations during production?

It simplifies purification if production levels are very high. Signup and view all the answers

What was the significance of the discovery of Penicillium notatum in 1928?

It killed bacteria by producing a bactericidal substance. Signup and view all the answers

How does penicillin disrupt bacterial growth?

By interfering with cell wall synthesis. Signup and view all the answers

Which granted Howard Florey and Ernst Chain a Nobel Prize?

Their work in purifying and testing penicillin. Signup and view all the answers

What kind of ring structure is crucial to the effectiveness of penicillin?

Beta-lactam ring Signup and view all the answers

Why must strains of penicillium be carefully selected for industrial production?

To enhance their ability to produce penicillin under harsh conditions. Signup and view all the answers

What is the purpose of creating mutant spores in the industrial production of penicillin?

To identify strains that produce more penicillin. Signup and view all the answers

In which phase is penicillin produced during fungal growth?

During the Idiophase. Signup and view all the answers

How does penicillin affect gram-positive bacteria specifically?

It disrupts their cell wall synthesis. Signup and view all the answers

What key process follows the addition of penicillin precursor phenylacetic acid in industrial production?

Initial growth continues to promote penicillin synthesis. Signup and view all the answers

What role do beta-lactamases play in relation to penicillin?

They hydrolyze penicillin, leading to resistance. Signup and view all the answers

What process is used to crystallize penicillin during its production?

Adding it to a solution of potassium in hot industrial methylated spirits. Signup and view all the answers

Which of the following statements about penicillin is false?

Penicillin only works on gram-negative bacteria. Signup and view all the answers

What is typically done with leftover solvents after penicillin production?

They are pumped to an onsite distillation facility for recovery and recycling. Signup and view all the answers

What undesirable effect did the lack of sufficient penicillin have on the first human trials?

The test subjects died without proper treatment. Signup and view all the answers

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.