Fed-Batch Biomolecule Production by Bacillus subtilis: A State of the Art Review

Ozturk, Sibel
Çalık, Pınar
Ozdamar, Tuncer H.
Bacillus subtilis is a highly promising production system for various biomolecules. This review begins with the algorithm of fed-batch operations (FBOs) and then illustrates the approaches to design the initial production medium and/or feed stream. Additionally, the feeding strategies developed with or without feedback control for fed-batch B. subtilis fermentations were compiled with a special emphasis on recombinant protein (r-protein) production. For biomolecule production by wild-type B. subtilis, due to the different intracellular production patterns, no consensus exists on the FBO strategy that gives the maximum productivity, whereas for r-protein production appropriate feeding strategies vary depending on the promoter used. Thus, we conclude that the B. subtilis community is still seeking an approved strong promoter and generalized FBO strategies.


Recombinant therapeutic protease production by Bacillus sp.
Korkmaz, Nuriye; Çalık, Pınar; Department of Chemical Engineering (2007)
The first aim of this study is the development of extracellular recombinant therapeutic protease streptokinase producing Bacillus sp., and the second aim is to determine fermentation characteristics for streptokinase production. In this context, the signal (pre-) DNA sequence of B.licheniformis (DSM1969) extracellular serine alkaline protease enzyme gene (subC: Acc. No. X03341) was ligated to 5’ end of the streptokinase gene (skc: Acc. No. S46536) by SOE (Gene Splicing by Overlap Extension) method through P...
Production of recombinant proteins by yeast cells
Celik, Eda; Çalık, Pınar (Elsevier BV, 2012-09-01)
Yeasts are widely used in production of recombinant proteins of medical or industrial interest. For each individual product, the most suitable expression system has to be identified and optimized, both on the genetic and fermentative level, by taking into account the properties of the product, the organism and the expression cassette. There is a wide range of important yeast expression hosts including the species Saccharomyces cerevisiae, Pichia pastoris, Hansenula polymorpha, Kluyveromyces lactis, Schizosa...
Obtaining durable enzyme powder via spray drying
Namaldı, Ayşegül; Adalı, Orhan; Department of Chemical Engineering (2005)
Serine alkaline protease (SAP, EC produced by Bacillus species, that are the microbioreactors within the bioreactors, is one of the major industrial enzymes. In this study, after production by Recombinant Bacillus subtilis (BGSC-1A751), carrying pHV1431::subc gene in the complex media and separation of solids, SAP was dried by using a spray drier. Experiments were performed to investigate the stabilization of SAP during spray drying and subsequent storage. Initially, the effect of air inlet tempe...
Codon optimization of xylA gene for recombinant glucose isomerase production in Pichia pastoris and fed-batch feeding strategies to fine-tune bioreactor performance
Ata, Ozge; Boy, Erdem; Gunes, Hande; Çalık, Pınar (Springer Science and Business Media LLC, 2015-05-01)
The objectives of this work are the optimization of the codons of xylA gene from Thermus thermophilus to enhance the production of recombinant glucose isomerase (rGI) in P. pastoris and to investigate the effects of feeding strategies on rGI production. Codons of xylA gene from T. thermophilus were optimized, ca. 30 % of the codons were replaced with those with higher frequencies according to the codon usage bias of P. pastoris, codon optimization resulted in a 2.4-fold higher rGI activity. To fine-tune bio...
Metabolic Flux Analysis for Recombinant Protein Production by Pichia pastoris Using Dual Carbon Sources: Effects of Methanol Feeding Rate
Celik, Eda; Çalık, Pınar; Oliver, Stephen G. (Wiley, 2010-02-01)
The intracellular metabolic fluxes through the central carbon pathways in the bioprocess for recombinant human erythropoietin (rHuEPO) production by Pichia pastoris (Mut(+)) were calculated. to investigate the metabolic effects of dual carbon sources (methanol/sorbitol) and the methanol feed rate, and to obtain a deeper understanding the regulatory circuitry of P. pastoris, using the established stoichiometry-based model containing 102 metabolites and 141 reaction fluxes. Four fed-batch operations with (MS-...
Citation Formats
S. Ozturk, P. Çalık, and T. H. Ozdamar, “Fed-Batch Biomolecule Production by Bacillus subtilis: A State of the Art Review,” TRENDS IN BIOTECHNOLOGY, pp. 329–345, 2016, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/39677.