title: Process optimization for an industrial-scale production of Diphtheria toxin by Corynebacterium diphtheriae PW8.
abstract: In this study, several parameters affecting the toxin production of Corynebacterium diphtheriae Parke Williams 8 (PW8) were investigated in detail. The comparison studies of amino acid profile in NZ Amine A-based medium (NZ medium) and beef digest-based medium (BD medium) suggested that an insufficient supply of amino acids was not responsible for low toxin yield observed in NZ medium. Supplementation of additional amino acids and growth promoting nutrient (in a form of yeast extract) into NZ medium enhanced only cell growth but not toxin production. Thus, BD medium was selected as the most suitable base medium for toxin production as it gave a significantly higher limit of flocculation (93 ± 0 Lf/ml) than NZ medium (46 ± 0 Lf/ml). Interestingly, a supplementation of 0.2% YE into BD medium resulted in a significant increase in growth as well as toxin production (235 ± 5 Lf/ml). In conclusion, consistently high toxin titer (174-239 Lf/ml) could be obtained from BD medium at a 5 L-scale production as long as 1) the protein content of BD medium was at least 24 g/L, 2) the iron content was below 0.15 ppm and 3) 0.2% YE was supplemented into the medium.
authors.affiliation: Department of Biological Products, The Government Pharmaceutical Organization (GPO), Bangkok, Thailand. Electronic address: boat5305190@gpo.or.th.
authors.forename: Maethichai
authors.initials: M
authors.lastname: Suwanpatcharakul
authors.affiliation: Department of Biological Products, The Government Pharmaceutical Organization (GPO), Bangkok, Thailand. Electronic address: unznaunz@gpo.or.th.
authors.forename: Chompunut
authors.initials: C
authors.lastname: Pakdeecharoen
authors.affiliation: Department of Biological Products, The Government Pharmaceutical Organization (GPO), Bangkok, Thailand. Electronic address: vsupitcha@gpo.or.th.
authors.forename: Supitcha
authors.initials: S
authors.lastname: Visuttitewin
authors.affiliation: Department of Biological Products, The Government Pharmaceutical Organization (GPO), Bangkok, Thailand. Electronic address: norapathp@gpo.or.th.
authors.forename: Norapath
authors.initials: N
authors.lastname: Pesirikan
authors.affiliation: Department of Biotechnology, Faculty of Science, Mahidol University, Bangkok, Thailand. Electronic address: somchai.cha@mahidol.ac.th.
authors.forename: Somchai
authors.initials: S
authors.lastname: Chauvatcharin
authors.affiliation: Department of Biotechnology, Faculty of Science, Mahidol University, Bangkok, Thailand. Electronic address: thunyarat.pon@mahidol.ac.th.
authors.forename: Thunyarat
authors.initials: T
authors.lastname: Pongtharangkul
mesh_terms: D003353:Corynebacterium diphtheriae / Q000254:growth & development*; D003470:Culture Media / Q000737:chemistry*; D004167:Diphtheria Toxin / Q000096:biosynthesis* / Q000302:isolation & purification*
chemical_list: D003470:Culture Media; D004167:Diphtheria Toxin
keywords: Corynebacterium diphtheriae; Diphtheria toxin; Papain beef digest medium