PRODUCTION OF PENICILLIN

“A 1957 fermentor (bioreactor) was used to grow PENICILLIUM MOULD “A 1957 fermentor (bioreactor) was used to grow PENICILLIUM MOULD. Penicillin is a secondary metabolite of certain species of Penicillium and is produced when growth of the fungus is inhibited by stress. It is not produced during active growth. Production is also limited by feedback in the synthesis pathway of penicillin.”

By ALEXANDER FLEMING as he was sorting petri dishes containing colonies of Staphylococcus. He noticed that plate was dotted with colonies. The zone around the mould was later identified as a rare strain of Penicillium notatum.

PENICILLIN PRODUCTION DEEP FERMENTATION methods, which were primarily development for the production of penicillin during the world war 2, gave rise to the development of antibiotics and contributed to the nascent biotechnology industry. Penicillin is a secondary metabolite, thus is only produced in the stationary phase. The industrial production of penicillin was generally classified into 2 processes : 1. Upstream processing 2. Downstream processing

Continue... UPSTREAM PROCESSING comprises of any technology that leads to the synthesis of a product and includes : exploration, development and production. DOWNSTREAM PROCESSING comprises extraction and purification of a biotechnological product from fermentation.

PROCESS OF PRODUCTION Like other industrial plant products, Penicillin production also has a process flow that begins with raw materials to downstream processes. MEDIUM FOR PRODUCTION ☆Carbon source – Corn steep liquor and glucose. ☆Salts – Magnesium Sulphate, Potassium Phosphate and Sodium Nitrates. HEAT STERILISATION Medium is sterilised at high heat and high pressure with the help of fermentor. The pressurised heat is used usually and medium is heated to 120°C at 30 psi.

FERMENTATION Usually done in a fed batch mode. The typical fermentation conditions are: ☆Temperature of 20- 24°C ☆PH conditions of 6.0- 6.5 ☆Pressure higher than the atmospheric pressure (1.02atm) ☆Sparging of air bubbles is necessary to provide sufficient oxygen for viability of the fungus. ☆The impeller is necessary to mix the culture medium. SEED CULTURE Seed culture is developed in Labs by addition of penicillin spores into a liquid medium and when it is grown to the acceptable amount it will be inoculated into the fermenter.

REMOVAL OF BIOMASS ☆Filtration is necessary at this point as bioseperation is required to remove the biomass from the culture such as fungus and other impurities from the medium containing penicillin product. ☆Rotary vacuum filter is commonly used. ☆Non oxidising acids such as Phosphoric acid are introduced as pH will be as high as 8.5. ADDING OF SOLVENT In order to dissolve the penicillin present in the filterate, organic solvents such as Amyl acetate or Butyl acetate are used. CENTRIFUGAL EXTRACTION Centrifugation is done to separate the solid waste from the liquid component which contains penicillin. Usually a Tubular bowl or Chamber bowl centrifuge is used.

EXTRACTION Penicillin dissolve in the solvent will now undergo a series of extraction process to obtain better purity of the penicillin product. FLUID BED DRYING Drying is necessary to remove any remaining moisture present in the powdered Penicillin salt. In this hot gas is pumped in from the Base of the chamber. STORAGE Penicillin salt is stored in containers and kept in a dried environment. It will then be polished and packed into various types of products such as liquid penicillin or penicillin in pills.