Improvement of a d-biotin-hyperproducing recombinant strain of Serratia marcescens. 1994

N Sakurai, and Y Imai, and M Masuda, and S Komatsubara, and T Tosa
Research Laboratory of Applied Biochemistry, Tanabe Seiyaku Co., Ltd., Osaka, Japan.

We previously reported that a recombinant strain, SB412(pLGM304), was constructed from acidomycin-resistant mutants of Serratia marcescens and produced 200 mg of d-biotin per liter of a medium containing sucrose and urea (Sakurai et al., 1993a, b). In the present work, we intended to improve the d-biotin production. Both ethionine and S-2-aminoethylcysteine resistances were added to the host strain SB412, producing d-biotin at 20 mg l-1, and a resultant strain, ETA23, producing it at 33 mg l-1, was obtained. Cells of ETA23 did not maintain pLGM304 stably after greater than 30 generations under non-selective culture conditions. A new recombinant plasmid, pLGM304P, was constructed so as to be composed of pLGM304 and the parB locus, a plasmid-stabilizing element. ETA23 stably maintained pLGM304P after 50 generations under non-selective culture conditions. ETA23(pLGM304) produced 250 mg l-1 of d-biotin in a shaking flask under batch culture conditions and 500 mg l-1 in a jar fermentor under fed-batch culture conditions.

UI MeSH Term Description Entries
D010957 Plasmids Extrachromosomal, usually CIRCULAR DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in GENETIC ENGINEERING as CLONING VECTORS. Episomes,Episome,Plasmid
D011994 Recombinant Proteins Proteins prepared by recombinant DNA technology. Biosynthetic Protein,Biosynthetic Proteins,DNA Recombinant Proteins,Recombinant Protein,Proteins, Biosynthetic,Proteins, Recombinant DNA,DNA Proteins, Recombinant,Protein, Biosynthetic,Protein, Recombinant,Proteins, DNA Recombinant,Proteins, Recombinant,Recombinant DNA Proteins,Recombinant Proteins, DNA
D003545 Cysteine A thiol-containing non-essential amino acid that is oxidized to form CYSTINE. Cysteine Hydrochloride,Half-Cystine,L-Cysteine,Zinc Cysteinate,Half Cystine,L Cysteine
D005001 Ethionine 2-Amino-4-(ethylthio)butyric acid. An antimetabolite and methionine antagonist that interferes with amino acid incorporation into proteins and with cellular ATP utilization. It also produces liver neoplasms.
D001710 Biotin A water-soluble, enzyme co-factor present in minute amounts in every living cell. It occurs mainly bound to proteins or polypeptides and is abundant in liver, kidney, pancreas, yeast, and milk. Vitamin H,Biodermatin,Biokur,Biotin Gelfert,Biotin Hermes,Biotin-Ratiopharm,Biotine Roche,Deacura,Gabunat,Medebiotin,Medobiotin,Rombellin,Biotin Ratiopharm,Gelfert, Biotin,Hermes, Biotin,Roche, Biotine
D012706 Serratia marcescens A species of gram-negative, facultatively anaerobic, rod-shaped bacteria found in soil, water, food, and clinical specimens. It is a prominent opportunistic pathogen for hospitalized patients.

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