Production of Clavulanic Acid by Streptomyces Clavuligerus Bacteria using Rapeseed Meal as The Source of Nitrogen
Ramin Shahrad Bejestani1, Fahimeh Nemati2 and Saeid Akbarzadeh Kolahi3*

1Herbal Medicines Research Center, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran (HMRC).

2Department Of Biotechnology, Faculty Of Advanced Sciences and Technology, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran (IAUPS).

3Department Of Pharmacology  and Toxicology, Faculty Of Pharmacy, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran (IAUPS).

*Corresponding Author E-mail: Saeidakbarzadeh4@gmail.com

Abstract: Clavulanic acid acts as an enzyme inhibitor like sulfactam and azobactam produced by Streptomyces Clavuligerus bacteria. This product plays a major role in pharmaceutical industry especially in producing Co-Amoxiclav. The fermentation stage plays a major role in producing secondary products. Nitrogen substrate is one of the main and most costly elements of the cultivation environment in this stage. Thus, utilizing affordable nitrogen resources with an acceptable level of output which is native and can be accesses with a constant quality is of great significance. The present research seeks to study the effect of various densities of rapeseed meal as the natural source of nitrogen and the cost in producing clavulanic acid. In this research, we utilized Streptomyces Clavuligerus strain to produce clavulanic acid. The main source of nitrogen which is soybean flour was replaced by rapeseed meal. Spore suspension was cultivated in seed ripening environment. Having formed Mycelium, it was then transferred to clavulanic production medium. The final product was cultivated for a period of 9 days in the temperature of 28  and the level of clavulanic produced was measured in certain days using spectrophotometer and HPLC. The samples collected from the cultivation medium were compared against one another in terms of the amount of clavulanic acid produced through spectrophotometer and HPLC. As it turned out, the highest amount of clavulanic acid was produced on the 8th day of cultivation in the medium containing 25 gr/L rapeseed meal as the source of nitrogen. This amount is equal to the amount produced in the main environment of clavulanic acid production which contained soybean flour as the source of nitrogen. Considering the amount of clavulanic acid produced in the medium containing rapeseed meal as the source of nitrogen and keeping in mind the favorable characters of rapeseed such as low price, availability, and the high rate of production, we may conclude that this product can be a good replica for the source of nitrogen in the absence of soybean flour.

Keywords: Clavulanic Acid; Rapeseed Meal; Nitrogen; Streptomyces Clavuligerus

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