2.1 Producing natural antibiotics
Natural antibiotics are complex chemicals which are synthesised stepwise by the bacteria or fungi that produce them in a series of enzyme-catalysed reactions. The starting compounds are usually products of the cell’s mtabolism – chemical reactions that allow a cell to obtain the energy and nutrients it needs to grow and survive. These essential compounds, or primary metabolites, are made in the exponential phase of growth. Antibiotics, however, are secondary metabolites , that is they are products of metabolism that are not essential for growth.
You might recall from Week 1 that bacteria and fungi produce antibiotics to prevent competing organisms using nutrients and other resources.
Why aren’t antibiotics produced during the exponential stage of growth?
Answer
The exponential stage is when abundant resources allow rapid growth, so only primary metabolites are made. During the stationary phase, competition for nutrients increases and resources are diverted away from growth to make antibiotics.
In manufacturing, pure cultures of antibiotic-producing bacteria and fungi are grown in huge bioreactors (containing thousands of litres) in a process known as batch fermentation . Batch fermentation favours antibiotic production by limiting the time that cells spend in the exponential growth phase. The antibiotic products are then harvested and purified.
As you will discover in Activity 1, this process was not always so streamlined.
Activity 1 Commercial production of penicillin – Part 1
Allow about 10 minutes
When Alexander Fleming accidentally discovered penicillin in 1928, he had no idea what to do with it or how to reproduce it. This was left for other researchers to do.
First, watch the video below about how penicillin was ‘rediscovered’ ten years later by Howard Florey and his Oxford-based research team.
Now answer the following questions, based on the video.
- What was the first key thing that Florey’s team achieved with penicillin?
- Why were British pharmaceutical companies reluctant to help develop penicillin?
- What did the American pharmaceutical companies achieve with penicillin?
Answer
- The penicillin was purified to a level that was safe for use in humans.
- In the late 1930s, British companies were prioritising the war effort.
- They increased production and isolated a more powerful Penicillium mould.
In the UK, Florey’s team had managed to purify penicillin and treat a bacterial infection. This was a major achievement, but the team was hampered by a lack of funding and equipment, and yields of the drug remained poor. After the move to the USA, the research picked up pace. By 1943, the production of penicillin was under way with the new, more powerful strain growing in a different medium – corn syrup. However, the production process was still inefficient and yields of penicillin remained low.
The second part of Activity 1 looks at the changes made to the manufacturing process that led to much higher yields of penicillin.
Activity 1 Commercial production of penicillin – Part 2
Allow about 10 minutes
The video below explains how the key to increased productivity was growing the Penicillium mould in a liquid, rather than as a layer at the bottom of a large flat-bottomed flask.
As you watch the video, consider the following questions.
- What was the advantage of a liquid medium?
- Why was it critical to control the level of oxygenation?
Discussion
- The liquid culture allowed more Penicillium to be grown and more penicillin to be produced.
- If the oxygen level is too low, Penicillium will die because it needs oxygen to grow. Too much oxygen can be toxic to fungi and bacteria – as it can be to humans.
OpenLearn - Understanding antibiotic resistance
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