Ampicillin Production

Antibiotic production
Ampicillin

1. Ampicillin Tendai Bere Washington Dendera Tanyaradzwa Ngara Nyasha Mudukuti

2. Introduction Antibiotics are specific chemical substances derived from or produced by living organisms that are capable of inhibiting the life processes of other organisms. Penicillins a group of closely related antibiotics used to treat a wide variety of bacterial infections occurring in the body

3. The first antibiotic was discovered in 1896 by Ernest Duchesne and "rediscovered" byAlexander Flemming in 1928 from the filamentous fungus Penicilium notatum . The antibiotic substance, named penicillin, was not purified until the 1940s (by Florey and Chain), just in time to be used at the end of the second world war Penicillin was the first important commercial product produced by an aerobic, submerged fermentation

4. Mechanism of Action Antibiotics can be selectively toxic by targeting such features as the bacterial cell wall, 70S ribosomes, and enzymes that are specific to bacteria. In this way the human eukaryotic cells are unaffected.

5. Mechanism of Action The walls of bacteria are made of a complex polymeric material called peptidoglycan. It contains both amino acids and amino sugars. The amino sugars are of two kinds N- acetylglucosamine (NAG) and N- acetylmuramic acid (NAM

6. Mechanism of action The beta-lactams all work by interfering with the synthesis of the bacterial cell wall by: disruption of mucopeptide syn­thesis 2)Penicillin can cause rapid lysis of the bacterial cell by inducing the action of bacterial autolysins ( mucopep­tide hydrolases). 3) penicillin exposes the cell to osmotic action and water passes from the hypotonic external environment into the interior of the cell.

7. Ampicillin prodrug is Broad - spectrum penicillin used against gram + ve and gram – ve bacteria - ampicillin is more active against enterococci, Listeria mono­cytogenes , and beta- Iactamase negative Haemophilus influenzae

8. Categories of Penicillin Two types: Biosynthetic penicillin is natural penicillin that is harvested from the mould itself through fermentation Semi-synthetic derivatives of penicillin - like Ampicillin, Penicillin V consist of the basic Penicillin structure, but have been purposefully modified chemically by removing the acyl group to leave 6-aminopenicillanic acid and then adding acyl groups that produce new properties

9. Antibiotic Production Antibiotics are produced on an industrial scale using a variety of fungi and bacteria Penicillin is produced by the fungus Penicillium chrysogenum penicillin is a secondary metabolite, so is only produced in the stationary phase. It requires a batch fermenter, and a fed batch process is normally used to prolong the stationary period and so increase production.

10. Bioreactor conditions optimum temperature – 25 -27ºC Fermentation process is aerobic volume fermenter is 40 –200 dm3 The first strain used to produce penicillin was Penicillin notatum , which produced 1 mg dm‐3 Today, using a different species (P. chrysogenum ) and a better extraction procedures the yield is 50 g dm‐3.

11. Downstream Processing Downstream processing is relatively easy since penicillin is secreted into the medium (to kill other cells), so there is no need to break open the fungal cells. However, the product needs to be very pure, since it being used as a therapeutic medical drug, so it is dissolved and then precipitated as a potassium salt to separate it from other substances in the medium.

12. The resulting penicillin (called penicillin G) can be chemically and enzymaticallymodified to make a variety of penicillinswith slightly different properties. These semi‐synthetic penicillinsinclude penicillin V, penicillin O, ampicillinand amoxycillin .

13. Ampicillin production Semi-synthetic derivative of penicillin consist of the basic Penicillin structure, but has been purposefully modified chemically by removing the acyl group to leave 6-aminopenicillanic acid and then adding an acyl group (amino group) allows the ampicillin to be effective against gram negative organisms as well as the gram positive organisms covered by penicillin makes ampicillin better as a 'broad spectrum antibiotic'

14. Fig2: Structure of Penicillin, Where “R” is the variable group

15. Fig 3: Structure of Ampicillin, with the added amino group

16. the product needs to be very pure, since it being used as a therapeutic medical drug, so it is dissolved and then precipitated as a potassium salt to separate it from other substances in the medium It is sold in liquid form, packaged into vials, for ready to use by injection

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