![]() Figure 2 shows sales volumes of different antibiotic classes for livestock, with sulfur-containing antibiotics (including nosiheptide) being one of the top sellers. Shown non-toxic at high dosages, nosiheptide is principally used for livestock applications. Nosiheptide and other thiopeptides’ mechanisms of action are a result of binding on the 50S ribosomal subunit which prevents selective protein synthesis. It exerts exceptional antibiotic activity in vitro and in a mouse model against critical Gram-positive pathogens such as methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococci (VRE) or Clostridium difficile. Nosiheptide ( Figure 1) is a sulfur-containing peptide antibiotic obtained through fermentation. Designing efficient antibiotic manufacturing processes is imperative. Optimal operation requires feedrate to be manipulated in such a way that the inhibitory mechanism of the substrate can be avoided, with significant nosiheptide yield improvement realized.Īntibiotics are essential pharmaceutical products in modern society, whose syntheses either require complex multistep chemical routes or make use of enzymatic pathways to obtain their complex molecular structures. The resultant large-scale NLP is solved using IPOPT. Orthogonal polynomials on finite elements are used to approximate the control and state trajectories allowing the continuous problem to be converted to a nonlinear program (NLP). A direct method for dynamic optimization (simultaneous strategy) is performed in each case to compute the optimal control trajectories. We then formulate a dynamic optimization problem for maximization of nosiheptide production for different constraints of batch duration and operability limits. Herein, we perform dynamic simulation over a broad range of possible feeding policies to understand and visualize the region of attainable reactor performances. A simplified mechanistic fed-batch fermentation model for nosiheptide production considers temperature- and pH-dependence of biomass growth, substrate consumption, nosiheptide production and oxygen mass transfer into the broth. Nosiheptide is a sulfur-containing peptide antibiotic, showing exceptional activity against critical pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE) with livestock applications that can be synthesized via fed-batch fermentation.
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