Optimum culture conditions for the epoxidation of cis-propenylphosphonate to fosfomycin by Cellvibrio gilvus.
Approximately 470 strains of various microorganisms were tested for their ability to epoxidize cis-propenylphosphonate (PPOH) to (-)-cis-1,2-epoxypropylphosphonate (fosfomycin, FOM). Cellvibrio gilvus KY 3412 was selected as the best strain. To obtain higher activity, FOM-resistant strains were derived by N-methyl-N'-nitro-N-nitrosoguanidine mutagenesis. Mutant KY 3413, showing ten times higher FOM resistance, was selected. The conditions for the conversion of PPOH to FOM during the cultivation of the mutant were optimized. The addition of both cobalt and vanadium ions to the culture medium greatly stimulated the conversion. Furthermore, when the pH was maintained at pH 8.0 during cultivation, the highest conversion was attained. The molar conversion yield of FOM was inversely dependent on the initial concentration of PPOH, that is, conversions of 100% at less than 0.05% PPOH and of 40% at 0.5% PPOH were attained after 5 days cultivation.
Tokyo Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., Japan.
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Aisaka
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Ohshiro
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T
Uwajima
D003035:Cobalt / Q000378:metabolism; D003470:Culture Media; D004852:Epoxy Compounds; D005578:Fosfomycin / Q000096:biosynthesis*; D006088:Gram-Negative Aerobic Bacteria / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D008769:Methylnitronitrosoguanidine; D016296:Mutagenesis; D009154:Mutation; D063065:Organophosphonates / Q000378:metabolism*; D009943:Organophosphorus Compounds / Q000378:metabolism*; D013678:Technology, Pharmaceutical; D014639:Vanadium / Q000378:metabolism
D003470:Culture Media; D004852:Epoxy Compounds; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D014639:Vanadium; D008769:Methylnitronitrosoguanidine; C074765:propenylphosphonic acid; D005578:Fosfomycin; D003035:Cobalt