Abstract

Antibiotics are a key pharmaceutical to inhibit growth or kill microorganisms. They represent a profitable market and, in particular, tetracycline has been listed as an essential medicine by the WHO. Therefore it is important to improve their production processes. Recently novel and traditional aqueous two-phase systems for the extraction have been developed with positive results. The present work performs an economic analysis of the production and recovery of tetracycline through the use of several ATPS through bioprocess modeling using specialized software (BioSolve, Biopharm Services Ltd, UK) to determine production costs per gram (CoG/g). First, a virtual model was constructed using published data on the recovery of tetracycline and extended to incorporate uncertainties. To determine how the model behaved, a sensitivity analysis and Monte Carlo simulations were performed. Results showed that ATPS formed by cholinium chloride/K3PO4 was the best option to recover tetracycline, as it had the lowest CoG/g (US$ 672.83/g), offered the highest recovery yield (92.42%), second best sample input capacity (45% of the ATPS composition) and one of the lowest materials contribution to cost. The ionic liquid-based method of ATPS is a promising alternative for recovering tetracycline from fermentation broth.

Highlights

  • Antibiotics are widely used to inhibit growth or kill infecting microorganisms in humans and animals

  • Its high CoG/g is explained by the low DSP yield which means that the cost is distributed across a small inventory of tetracycline, causing the CoG/g to increase

  • This research has demonstrated the capabilities of bioprocess modeling and economic analysis to compare and contrast novel and traditional recovery aqueous two phase systems (ATPS)-based techniques

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Summary

Introduction

Antibiotics are widely used to inhibit growth or kill infecting microorganisms in humans and animals. They represent a globally profitable market; in 2009 sales generated US$ 42 billion [1]. There are multiple types of antibiotics, for example β-lactams, cephalosporins, aminoglycosides, macrolides and tetracyclines (TC’s) [2]. Tetracyclines are bacteriostatic antimicrobials produced mainly through fermentation by the Streptomyces genre [3,4] and are considered broad spectrum antibiotics. They act by binding to ribosome regions and inhibit protein synthesis, preventing the growth of bacteria and, killing them [5]. Tetracycline is listed as an essential medicine by the World Health Organization [6], which makes identifying effective and economic routes for its production a priority

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