title: Fed-Batch Biomolecule Production by Bacillus subtilis: A State of the Art Review.
abstract: 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.
authors.affiliation: Industrial Biotechnology and Metabolic Engineering Laboratory, Department of Chemical Engineering, Middle East Technical University, 06800 Ankara, Turkey; Graduate School of Natural and Applied Sciences, Department of Biotechnology, Middle East Technical University, 06800 Ankara, Turkey.
authors.forename: Sibel
authors.initials: S
authors.lastname: Ÿztürk
authors.affiliation: Industrial Biotechnology and Metabolic Engineering Laboratory, Department of Chemical Engineering, Middle East Technical University, 06800 Ankara, Turkey; Graduate School of Natural and Applied Sciences, Department of Biotechnology, Middle East Technical University, 06800 Ankara, Turkey. Electronic address: pcalik@metu.edu.tr.
authors.forename: Pınar
authors.initials: P
authors.lastname: Ÿalık
authors.affiliation: Biochemical Reaction Engineering Laboratory, Chemical Engineering Department, Ankara University, 06100 TandoĿan, Ankara, Turkey.
authors.forename: Tunçer H
authors.initials: TH
authors.lastname: Ÿzdamar
mesh_terms: D001412:Bacillus subtilis / Q000254:growth & development* / Q000378:metabolism*; D061249:Batch Cell Culture Techniques / Q000379:methods*; D001688:Biological Products / Q000378:metabolism*; D003470:Culture Media / Q000737:chemistry; D015964:Gene Expression Regulation, Bacterial; D011994:Recombinant Proteins / Q000378:metabolism
chemical_list: D001688:Biological Products; D003470:Culture Media; D011994:Recombinant Proteins
keywords: Bacillus subtilis; algorithm; biomolecule; fed batch; feeding strategy; recombinant protein