Bioprocess development for serine alkaline protease production: A review

Çalık, Pınar
Ozdamar, TH
This work is the result of the convergence of the research in biochemical reaction engineering and metabolic flux analysis for serine alkaline protease (SAP) production. The genus Bacillus includes a variety of industrially important species that are known to secrete a large number of extracellular proteases and are used among many species as producer of SAP enzyme. Therefore, in the first part of the present article an overview to serine alkaline protease and regulation of its synthesis and secretion in Bacillus is presented. In the second part, a detailed review of the published information on the bioprocess medium design and bioreactor operation parameters are discussed in relation to the concentrations of the byproducts, i.e. neutral protease, amylase, amino acids, organic acids and alcohols. In the third part, papers on metabolic flux analysis for SAP are reviewed with the emphasis on SAP overproduction potential of the Bacillus licheniformis, the effect of oxygen transfer on the bioreaction-network fluxes and the need for oxygen transfer strategies. The metabolic bottlenecks and strategies for increasing the yield and selectivity of SAP fermentation process are discussed.


Metabolic flux analyses for serine alkaline protease production
Çalık, Pınar; Ozdamar, TH (2000-12-01)
The intracellular metabolic fluxes through the central carbon pathways in Bacillus licheniformis in serine alkaline protease (SAP) production were calculated to predict the potential strategies for increasing the performance of the bacilli, by using two optimization approaches, i.e. the theoretical data-based (TDA) and the theoretical data-based capacity (TDC) analyses based on respectively minimum in-vivo SAP accumulation rate and maximum SAP synthesis rate assumptions, at low-, medium, and high-oxygen tra...
Metabolic flux analysis for serine alkaline protease fermentation by Bacillus licheniformis in a defined medium: Effects of the oxygen transfer rate
Çalık, Pınar; Ozdamar, TH (1999-07-01)
The metabolic fluxes through the central carbon pathways in the bioprocess for serine alkaline protease (SAP) production by Bacillus licheniformis were calculated by the metabolic flux-based stoichiometric model based on the proposed metabolic network that contains 102 metabolites and 133 reaction fluxes using the time profiles of citrate, dry cell, organic acids, amino acids, and SAP as the constraints. The model was solved by minimizing the SAP accumulation rate in the cell, The effects of the oxygen-tran...
Serine alkaline protease overproduction capacity of Bacillus licheniformis
Çalık, Pınar; Ozdamar, TH (2000-01-01)
A comprehensive metabolic network that considers 147 reaction fluxes and 105 metabolites is used in a mass-Aux-balance-based stoichiometric model for Bacillus licheniformis for serine alkaline protease (SAP) overproduction. The theoretical capacity analysis leading to optimized SAP overproduction was carried out by using a linear constrained optimization technique for several specific growth rates and the variation of the fluxes were calculated by fixing the sole carbon source citrate's uptake rate at 10 mm...
Investigation of bioreactor operation conditions for serine alkaline protease production by Bacillus subtilis
Özdemir, Elif; Çalık, Pınar; Department of Chemical Engineering (2003)
In this study, complex medium was designed for increasing serine alkaline protease (SAP) production by recombinant Bacillus sp. In this context, the effects of glucose, sucrose, inorganic nitrogen source, casein, defatted soybean, and molasses and their concerted effects were investigated in agitation (N=200 min"1) and heating rate (T=37°C) controlled laboratory scale bioreactors. For this purpose, experiments were started by microorganism selection. It was found that, most suitable microorganism for comple...
Bioreaction network flux analysis for industrial microorganisms: A review
Çalık, Pınar (Walter de Gruyter GmbH, 2002-01-01)
This review focuses on the analysis of the bioreaction networks of the microorgansims used in fermentation processes, by metabolic flux analysis that is the novel tool of biochemical reaction engineering, required for the quantitative analysis of cell metabolism which is under the control of the cell physiology. Metabolic flux analysis (MFA) is based on calculation of intracellular reaction network rates through various reaction pathways either theoretical or by using elaborate experimental data on uptake, ...
Citation Formats
P. Çalık and T. Ozdamar, “Bioprocess development for serine alkaline protease production: A review,” REVIEWS IN CHEMICAL ENGINEERING, pp. 1–62, 2001, Accessed: 00, 2020. [Online]. Available: