Abstract: A membrane filter of 0.025 to 0.05 .mu. in pore size is treated by passing the solution of a water-soluble high molecular substance such as albumin, dextran, polyvinylpyrrolidone, polysorbate 80, gelatin or the like through the membrane filter. Employing the filter thus treated, the solution of a physiologically active substance of human origin such as human growth hormone, kallikrein, trypsin inhibitor, epidermal growth factor, leucocyte interferon etc. is filtered at high recovery rate of the active substance avoiding the adsorption of the active substance onto the filter. By the filtration, harmful viruses such as Creutzfeldt-Jacob disease pathogen which may exist in the physiologically active substance can be removed.

Abstract: This invention relates to a process for the microbiological production of compounds containing a terminal hydroxyl or epoxy group from an aliphatic substrate or a substrate with an aliphatic side chain, using microorganisms genetically engineered so that they have retained their capacity to perform the terminal oxidation of the substrate, but are no longer able to convert the resulting oxidation product further to any significant extent. Preferred substrates are n-alkanes, n-alkenes, and n-alkadienes containing 6-12 carbon atoms. Preferred micro-organisms are genetically engineered Pseudomonas oleovorans and Pseudomonas putida strains lacking an active plasmidic alkanol-dehydrogenase gene. The invention also relates to micro-organisms thus genetically engineered.

Abstract: Method for the site specific genomic modification of yeasts of the genus Pichia and novel DNA sequences useful therefore are provided. Pichia is transformed with a serially arranged linear DNA fragment comprising first and second insertable DNA fragments, which flank a marker gene. The insertable DNA sequences are homologous to defined portions of the Pichia genome and integrate by recombination at such defined sites. The resulting transformed organism contains the marker gene and any additional DNA sequences which are positioned between the insertable DNA fragments. In addition, the resulting transformed organism has either a disrupted or deleted sequence at the site of the genomic modification. Enhanced production of heterologous gene products is observed when using as the host for expression strains in which the alcohol oxidase gene has been disrupted. Upon disruption of the primary alcohol oxidase gene of Pichia, the existence of a second alcohol oxidase gene in Pichia was also discovered.

Abstract: Method for the site specific genomic modification of yeasts of the genus Pichia and novel DNA sequences useful therefore are provided. Pichia is transformed with a serially arranged linear DNA fragment comprising first and second insertable DNA fragments, which flank a marker gene. The insertable DNA sequences are homologous to defined portions of the Pichia genome and integrate by recombination at such defined sites. The resulting transformed organism contains the marker gene and any additional DNA sequences which are positioned between the insertable DNA fragments. In addition, the resulting transformed organism has either a disrupted or deleted sequence at the site of the genomic modification. Enhanced production of heterologous gene products is observed when using as the host for expression strains in which the alcohol oxidase gene has been disrupted. Upon disruption of the primary alcohol oxidase gene of Pichia, the existence of a second alcohol oxidase gene in Pichia was also discovered.