Abstract
BackgroundShikimic acid, the sole chemical building block for the antiviral drug oseltamivir (Tamiflu®), is one of the potent pharmaceutical intermediates with three chiral centers. Here we report a metabolically engineered recombinant Bacillus megaterium strain with aroE (shikimate dehydrogenase) overexpression for the production of shikimic acid.ResultsIn a 7 L bioreactor, 4.2 g/L shikimic acid was obtained using the recombinant strain over 0.53 g/L with the wild type. The enhancement of total shikimate dehydrogenase activity was 2.13-fold higher than the wild type. Maximum yield of shikimic acid (12.54 g/L) was obtained with fructose as carbon source. It was isolated from the fermentation broth using amberlite IRA-400 resin and 89 % purity of the product was achieved.ConclusionThis will add up a new organism in the armory for the fermentation based production which is better over plant based extraction and chemical synthesis of shikimic acid.Electronic supplementary materialThe online version of this article (doi:10.1186/s12934-015-0251-3) contains supplementary material, which is available to authorized users.
Highlights
Shikimic acid, the sole chemical building block for the antiviral drug oseltamivir (Tamiflu®), is one of the potent pharmaceutical intermediates with three chiral centers
We have developed a modified strain of Bacillus megaterium with aroE overexpression for the production of shikimic acid (Fig. 1)
Expression profile of shikimate dehydrogenase and PMF based identification To generate an aroE overexpression mutant of B. megaterium, the aroE gene from B. subtilis was cloned into pWH1520 vector
Summary
The sole chemical building block for the antiviral drug oseltamivir (Tamiflu®), is one of the potent pharmaceutical intermediates with three chiral centers. Due to its unique structure, it has been used as the building block for the synthesis of several biologically active compounds such as antibiotics, antitumor agents [2], antithrombotic agents [3, 4], and vitamins etc. It has been used in the organic synthesis and cosmetic industry [5]. Shikimate is mainly produced by chemical synthesis or extraction from the fruit of Illicium spp These processes are complicated with the high cost and/or limitations of raw materials making it difficult to meet the increasing worldwide requirements due to the global pandemic of influenza [6]. Microbial fermentation is regarded as a potential alternative for large scale production considering the increasing demand of shikimate [7]
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