Abstract: The invention provides methods of manufacturing oils and oil-based products such as transportation fuels, industrial chemicals, edible oils, lubricants and plastics using sugar cane, sugar beets, and cane/beet agricultural processing byproducts as a feedstock for bioproduction processes. The disclosed processes utilize oil-bearing microbes as a conversion technology to convert chemical energy produced by sugar cane and sugar beets into energy-containing oils and oil derivatives. Also provided herein are oil-bearing microbes containing one or more exogenous sucrose utilization genes.

Abstract: The present invention is directed to methods and compositions for microbial based production of pravastatin. The compositions of the invention include novel strains of microorganisms that are capable of efficiently hydroxylating compactin (ML-236 B) resulting in production of pravastatin. In particular, the microorganisms of the invention are genetically engineered to express both cytochrome P-450 and the fdxshe or fdxshe-like protein. The invention further relates to the use of such microorganisms in processes designed for production of pravastatin for use in treatment of disease such as hypercholesterolemia and hyperlipidemia.

Abstract: The present invention relates to polypeptides that have an activity corresponding to at least one activity of the SEC61 polypeptide, polynucleotides encoding these polypeptides and the use thereof in the preparation of host cells suitable for production of a polypeptide of interest. Such host cells may have an increased capacity to secrete a polypeptide of interest.

Abstract: The present invention provides cells having more than two drug resistance genes and at least two different resistance genes that have been recombined into the chromosome of a cell. It also teaches the processes for preparing cells by recombining two or more different drug resistance genes into the chromosome of a cell. The invention further shows a screening method using the cells of described herein that may be used to accomplish high throughput screening of, among other things, natural products and/or whole cells isolated from the environment.

Abstract: Four new Penicillium spp. isolates (NRRL 21966, NRRL 21967, NRRL 21968, and NRRL 21969) are capable of essentially quantitative conversion of native alternan to a polymeric modified form having a lower apparent molecular weight than native alternan. A fifth isolate (NRRL 30489) obtained from a survey of deposited organisms and classified as a Penicillium subgenus Biverticillium has the same ability. The modified alternan has rheological properties similar to ultrasonicated alternan and is produced without the expense of ultrasonication. It would have utility as a substitute for gum arabic for uses such as bulking agents and extenders in foods and cosmetics.

Abstract: The present invention relates to isolated promoter DNA sequences, to DNA constructs, vectors, and host cells comprising these promoters in operative association with coding sequences. The present invention also relates to methods for expressing a gene and/or producing a biological compound using the new promoters isolated. The present invention also relates to methods for altering the transcription level and/or regulation of an endogenous gene using the new promoter of the invention.

Abstract: The subject invention relates to the identification of a gene involved in the elongation of polyunsaturated fatty acids containing unsaturation at the carbon 9 position (i.e., “?9-elongase”) and to uses thereof. In particular, ?9-elongase may be utilized, for example, in the conversion of linoleic acid (LA, 18:2n-6) to eicosadienoic acid (EDA, 20:2n-6). The production of dihomo-?-linolenic acid (DGLA, 20:3n-6) from eicosadienoic acid (EDA, 20:2n-6), and arachidonic acid (AA, 20:4n-6) from dihomo-?-linolenic acid (DGLA, 20:3n-6) is then catalyzed by ?8-desaturase and ?5-desaturase, respectively. AA or polyunsaturated fatty acids produced therefrom may be added to pharmaceutical compositions, nutritional compositions, animal feeds, as well as other products such as cosmetics.

Abstract: The present invention relates to fungal host cells that are transformed with a nucleic acid construct encoding a fungal oxygen-binding proteins or fragments thereof that comprise the oxygen-binding domain. Upon transformation of the host cell with the construct, the oxygen-binding protein confers to the host cell improved fermentation characteristics as compared to untransformed host cells. These characteristics include e.g. increases in oxygen uptake rates, biomass densities, volumetric productivities and/or product yields. The invention further relates to fermentation processes in which the host cells are used and to fungal oxygen binding proteins, in particular fungal flavohemoglobins and hemoglobin domains, and to nucleotides sequences encoding these proteins.

Abstract: The invention relates to a nucleotide sequence comprising: a synonymous nucleotide coding sequence with optimized codon frequency such that a native codon has been exchanged with a synonymous codon, said synonymous codon encoding the same amino acid as the native codon and having a higher frequency in codon usage as defined in Table 1 than the native codon; and optionally said nucleotide sequence comprises control sequences such as: one translational termination sequence orientated in 5? towards 3? direction selected from the following list of sequences: TAAG, TAGA and TAAA, preferably TAAA, and/or one translational initiator coding sequence orientated in 5? towards 3? direction selected from the following list of sequences: gctnccyyc, using ambiguity codes for nucleotides: v (A/C/G); n (A/C/G/T), preferably 5?-GCT TCC TTC-3?.

Abstract: The present invention relates to novel micro-organism, Penicillium funiculosum, to new enzymes mixture obtained from it and nucleic acid sequences thereto.

Abstract: The present invention relates to novel phytases, in particular, of fungal origin, and also to their respective methods of production. The present invention relates more particularly to novel phytases derived from fungi of the Penicillium genus, in particular of the Penicillium sp. CBS 109899 strain, and also to the polynucleotides encoding these phytases. The invention also relates to vectors containing the polynucleotides, and to transformed host organisms expressing the phytases.

Abstract: The present invention relates to codon-optimized xylanase coding sequences and the expression of xylanases in microbes and yeast. The invention further relates to using multiple copies of the xylanase expression construct for high levels of protein expression. The invention also relates to the use of xylanases as feed or food additives. The invention also relates to methods of expression of enzymes to increase thermotolerance by expressing them in organisms that glycosylate proteins compared to expression that the same enzyme without the glycosylation. Further, the invention relates to methods of preparing feed, enzyme feed additives, and methods of reducing the feed conversion ration or increasing weight gain of animals.

Abstract: The present invention is to provide a low molecular weight hyaluronan by acting a hyaluronidase derived from a microorganism belonging to the genus Penicillium on a hyaluronan and a process for preparing the same, and an enzyme composition which can be suitably used for the preparation of the low molecular weight hyaluronan.

Abstract: The present invention relates to isolated nucleic acid molecules encoding nitric oxide synthases. The isolated nucleic acid molecules and their encoded protein or polypeptides are useful in methods for attaching a nitrogen group to a target moiety of a compound and for synthesizing a nitrogen-modified compound in a transgenic host cell. The present invention also relates to expression systems and host cells containing the nucleic acids of the present invention, as well as a method of recombinantly producing the nitric oxide synthases of the present invention.

Abstract: The subject invention relates to the identification of four genes involved in the elongation of polyunsaturated acids (i.e., “elongases”) and to uses thereof. Two of these genes are also involved in the elongation of monounsaturated fatty acids. In particular, elongase is utilized in the conversion of gamma linolenic acid (GLA) to dihomogamma linolenic acid (DGLA) and in the conversion of DGLA or 20:4n-3 to eicosapentaenoic acid (EPA). DGLA may be utilized in the production of polyunsaturated fatty acids, such as arachidonic acid (AA), docosahexaenoic acid (DHA), EPA, adrenic acid, ?6-docosapentaenoic acid or ?3-docosapentaenoic acid which may be added to pharmaceutical compositions, nutritional compositions, animal feeds, as well as other products such as cosmetics.

Abstract: The present invention relates to a novel microorganism and a method for producing fructooligosaccharides and neofructooligosaccharides. More particularly, the present invention relates to Penicillium citrinum KCTC 10225BP of soil origin which produces fructosyl transferase and hydrolyzes sucrose into fructooligosaccharides of the following formula I: in which n is integer of 1 to 5, G represents glucose and F represents fructose, and neofructooligosaccharides of the following formula II: in which n is integer of 1 to 5, G and F are defined as above, at the same time using the fructosyl transferase, and to a method for producing simultaneously fructooligosaccharides and neofructooligosaccharides using said microorganism.

Abstract: DNA sequences obtained from S. clavuligerus ATCC 27064, recombinant vectors incorporating such sequences and hosts transformed with such vectors are disclosed. The DNA comprises one or more genes coding for one or more enzymes involved in the biosynthesis of penicillin and cephalosporin ?-lactams and such enzymes are expressed by hosts into which the recombinant vectors are transformed. The DNA and the enzymes encoded thereby have utility in the preparation of penicillins and cephalosporins, both known and novel, possessing pharmacological, especially antimicrobial, activity.

Abstract: The present invention relates to increasing the production of a protein of interest from a fugal host. The invention discloses nucleotide sequences comprising, a regulatory region in operative association with xylanase secretion sequence and a gene of interest. The gene of interest encodes a protein selected from a pharmaceutical, nutraceutical, industrial, animal feed, food additive and an enzyme. Preferably, the gene of interest encodes a cellulase, hernicellulase, a lignin degrading enzyme, pectinase, protease, or peroxidase. The present invention also relates to vectors and hosts comprising these nucleic acid sequences, and to methods for the production of a protein of interest.

Abstract: The subject invention relates to the identification of several genes involved in the elongation of polyunsaturated acids (i.e., “elongases”) and to uses thereof. At least two of these genes are also involved in the elongation of monounsaturated fatty acids. In particular, elongase is utilized in the conversion of gamma linolenic acid (GLA) to dihomogama linolenic acid (DGLA) and in the conversion of DGLA or 20:4n-3 to eicosapentaenoic acid (EPA). DGLA may be utilized in the production of polyunsaturated fatty acids, such as arachiodonic acid (AA), docosahexaenoic acid (DHA), EPA, adrenic acid, ?6-docosapentaenoic acid or ?3-docosapentaenoic acid which may be added to pharmaceutical compositions, nutritional compositions, animal feeds, as well as other products such as cosmetics.

Abstract: A mutated expandase enzyme having higher activity on penicillin G is provided to produce phenylacetyl-7-aminodeacetoxycephalosporanic acid (7-ADCA), which mutated expandase enzyme has one or more amino acid substitutions selected form M73T, S79E, V275I, L277K, C281Y, G300V, N304K, I305L and I305M.

Abstract: The invention relates to a recombinant DNA molecule which comprises genes for biosynthesizing acarbose and homologous pseudo-oligosaccharides; to oligonucleotide primers for the PCR amplification of the molecule; to proteins which can be obtained by expressing the genes located on a molecule; to vectors and host cells which comprise the above-mentioned DNA molecule; to proteins which are encoded by the DNA molecule; to proteins which are expressed by means of said vectors in said host cells; to processes for preparing acarbose by introducing the characterized genes into appropriate host organisms and/or eliminating these genes from the host organisms; to processes for completing the gene cluster of genes for biosynthesizing acarbose, to processes for isolating analogous gene clusters in organisms other than Streptomyces glaucescens GLA.

Abstract: The present invention relates to a novel microorganism and a method for producing fructooligosaccharides and neofructooligosaccharides.

Abstract: A mutated expandase enzyme having higher activity on penicillin G is provided to produce phenylacetyl-7-aminodeacetoxycephalosporanic acid (7-ADCA), which mutated expandase enzyme has one or more amino acid substitutions selected form M73T, S79E, V275I, L277K, C281Y, G300V, N304K, I305L and I305M.

Abstract: The present invention relates to processes for the microbial oxidation of bicyclic heteroaromatic compounds which comprise contacting these compounds with a microorganism, or a suitable mutant thereof, and incubating the resulting mixture under conditions sufficient to yield an amount of their respective carboxylic acids. The present processes optionally further comprise the isolation and purification of the product carboxylic acids.

Abstract: A mutated expandase enzyme having higher activity on penicillin G is provided to produce phenylacetyl-7-aminodeacetoxycephalosporanic acid (7-ADCA), which mutated expandase enzyme has one or more amino acid substitutions selected form M73T, S79E, V275I, L277K, C281Y, G300V, N304K, I305L and I305M.

Abstract: The subject invention relates to the identification of several genes involved in the elongation of polyunsaturated acids (i.e., “elongases”) and to uses thereof. At least two of these genes are also involved in the elongation of monounsaturated fatty acids. In particular, elongase is utilized in the conversion of gamma linolenic acid (GLA) to dihomogamma linolenic acid (DGLA) and in the conversion of AA to adrenic acid (ADA), or eicosapentaenoic acid (EPA) to &ohgr;3-docosapentaenoic acid (DPA). DGLA may be utilized in the production of polyunsaturated fatty acids, such as arachidonic acid (AA), docosahexaenoic acid (DHA), EPA, adrenic acid, &ohgr;6-docosapentaenoic acid or &ohgr;3-docosapentaenoic acid which may be added to pharmaceutical compositions, nutritional compositions, animal feeds, as well as other products such as cosmetics.

Abstract: The present invention discloses novel amdS genes from fungi previously not known to contain and amdS gene, such as Aspergillus niger and Penicillium chrysogenum. The novel amdS genes can be used as homologous selectable marker genes in the transformation of these fungi. Alternatively, the cloned amdS genes can be used to inactivate the endogenous copy of the gene in order to reduce the background in transformation experiments.

Abstract: The invention concerns a new tool for efficient mutagenesis enabling the generation of a collection of mutants in fungi by random insertion of a characterized Fusarium oxysporum Impala transposon in the genome of said fungi. The invention also concerns the resulting mutants.

Abstract: To provide a semaphorin inhibitor; a peripheral or central nerve regeneration promoter which contains said semaphorin inhibitor as an active ingredient; and a preventive or remedy for a neuropathic disease and a neurodegenerative disease containing said nerve regeneration promoter, or the like.

Abstract: Nucleic acids for detecting Aspergillus species and other filamentous fungi are provided. Unique internal transcribed spacer 2; coding regions permit the development of nucleic acid probes specific for five different species of Aspergillus, three species of Fusarium, four species of Mucor, two species of Penecillium, five species of Rhizopus, one species of Rhizomucor, as well as probes for Absidia corymbifera, Cunninghamella elagans, Pseudallescheria boydii, and Sporothrix schenkii. The invention thereby provides methods for the species-specific detection and diagnosis of infection by Aspergillus, Fusarium, Mucor, Penecillium, Rhizopus, Rhizomucor, Absidia, Cunninghamella, Pseudallescheria or Sporothrix in a subject. Furthermore, genus-specific probes are also provided for Aspergillus, Fusarium and Mucor, in addition to an all-fungus nucleic acid probe.

Abstract: A novel DNA is provided which encodes an enzyme having phytase activity isolated from Penicillium. Also provided for is a method of isolating DNA encoding an enzyme having phytase activity from organisms which possess such DNA, transformation of the DNA into a suitable host organism, expression of the transformed DNA and the use of the expressed phytase protein in feed as a supplement.

Abstract: The present invention relates to novel micro-organism, Penicillium funiculosum, to new enzymes mixture obtained from it and nucleic acid sequences thereto.

Abstract: An isolated DNA having the promoter sequence of the hex gene of P. chrysogenum or a DNA fragment that is hybridizable to the complement of the promoter sequence under stringent conditions and is capable of directing expression of DNA downstream of the fragment in P. chrysogenum. Also a process for promoting expression of a coding sequence of interest in a microorganism using the isolated DNA and a process to block expression of a gene of interest in a microorganism using the isolated DNA are disclosed.

Abstract: The present invention relates to a novel microorganism and a method for producing fructooligosaccharides and neofructooligosaccharides.

Abstract: The present invention relates to a novel micro-organism, Penicillium funiculosum, to a new enzymes mixture obtained from it, and nucleic acid sequences encoding such enzymes.

Abstract: The invention relates to an isolated Penicillium strain capable of eliminating a nitroaromatic compound by mineralization and a microbiological method for eliminating a nitroaromatic compound present in a solution or in a soil.

Abstract: The present invention relates to a transcription factor found in filamentous fungi, especially in Aspergillii, DNA sequences coding for said factor, its transformation into and expression in fungal host organisms, and the use of said factor in such hosts for increasing the expression of a polypeptide of interest being produced by said host.

Abstract: The present invention relates to a modified enzyme of a non-heme iron (II) dependent family of oxygenases and oxidases which renders the enzyme dependent on bicarbonate for activity. In a preferred embodiment, the modification is an arginine, lysine, or other amino acid that is two amino acid residues upstream of a histidine residue that is an iron ligand in the enzyme and is one of the histidine residues of the 2-histidine-1-aspartic acid trifacial motif. In particular, the modified enzymes are isopenicillin N synthetase, deacetoxycephalosporin C synthetase, and deacetoxycephalosporin C synthetase/deacetylcephalosporin C synthetase which are used to make antibiotics. The present invention further provides a method for making antibiotics using a modified enzyme such as isopenicillin N synthetase, deacetoxycephalosporin C synthetase, and deacetoxycephalosporin C synthetase/deacetylcephalosporin C synthetase wherein the modification renders the enzyme dependent on bicarbonate for activity.

Abstract: This invention relates to the isochroman compound of formula (I) and its pharmaceutically acceptable salts, which are useful as an amyloid aggregation inhibitor and for treating Alzheimer's disease. This invention also relates to processes for producing the isochroman compound, which comprises cultivating Penicillium simplicissimum FERM BP-6357 and then isolating the isochroman compound from the fermentation broth. The present invention also relates to a pharmaceutical composition comprising the isochroman compound.

Abstract: A process for site-directed integration of multiple copies of a gene in a mould is provided, which comprises transforming a mould cell containing in its chromosomal DNA a restriction site for a rare-cutting endonuclease, e.g., I-Scel, preferably introduced at a desired locus, e.g., within a selectable marker gene or in the neighborhood thereof, with a piece of DNA comprising multiple copies of at least one expressible gene comprising at least one structural gene encoding a desired protein, surrounded by two DNA fragments homologous to part of the DNA upstream and downstream, and in the neighborhood, of said restriction site, while during the transformation of the mould the presence of the rare-cutting endonuclease is provided, followed by selecting or screening for a mould cell in which the multiple gene copies of said expressible gene are inserted into the chromosomal DNA of the mould.

Abstract: The present invention relates to filamentous fungi that comprise in their genomes at least two substantially homologous DNA domains which are suitable for integration of one or more copies of a recombinant DNA molecule and wherein at least two of these DNA domains comprise an integrated copy of a recombinant DNA molecule. The invention also relates to methods for preparing such filamentous fungi and for further multiplying the DNA domains with integrated recombinant DNA molecules through gene conversion or amplification.

Abstract: Fungi and bacteria can be detected and rapidly quantified by using the nucleotide sequences taught here that are specific to the particular species or group of species of fungi or bacteria. Use of the sequences can be made with fluorescent labeled probes, such as in the TaqMan™ system which produces real time detection of polymerase chain reaction (PCR) products. Other methods of detection and quantification based on these sequences include hybridization, conventional PCR or other molecular techniques.

Abstract: A novel microorganism, Penicillium citrinum CCRC 930024 and a process of using the microorganism for the production of compactin comprising cultivating Penicillium citrinum CCRC 930024 in a fermentation medium and recovering compactin from the fermentation broth are disclosed.

Abstract: The invention relates to promoters of the genes glutamate dehydrogenase, &bgr;-acetylhexosaminidase and &ggr;-actin and their use in systems of expression, secretion and anti-sense of filamentary fungi. The invention also relates to the use of the promoters of the genes which code: (I) glutamate dehydrogenase NADP depending (EC.1.4.1.4) of Penicillium chrysogenum, (II) &ggr;-N-actylhexosaminidase (EC.3.2.1.52) of Penicillium chrysogenum and (III) &ggr;-actin of Penicillium chrysogenum and Acrimonium chrysogenum, which can be used for the construction of potent vectors of expression and secretion useful both for P. chrysogenum and for A. chrysogenum and related species. These promoters can also be used for blocking the genic expression through anti-sense construction. Under the control of the above mentioned promoters, it is possible to conduct the expression of other genes in filamentary fungi, thereby increasing the production of antibiotics and/or proteins inherent to the same.

Abstract: The present invention provides methods and compositions for producing and screening combinatorial metabolic libraries of multimeric proteins. The present invention relies on the use of filamentous fingal heterokaryons that are produced using two or more parent strains into which a population of heterologous nucleic acids encoding components of a metabolic pathway have been introduced.

Abstract: The invention includes novel fusion nucleic acids encoding fusion polypeptides which when expressed in a filamentous fungus result in the expression of fusion polypeptides. The fusion nucleic acids comprise four nucleic acids which encode a fusion polypeptide comprising first, second, third and fourth amino acid sequences. The first nucleic acid encodes a signal polypeptide functional as a secretory sequence in a first filamentous fungus. The second nucleic acid encodes a secreted polypeptide or functional portion thereof which is normally secreted from the same filamentous fungus or a second filamentous fungus. The third nucleic acid encodes a cleavable linker while the fourth nucleic acid comprises at least two nucleic acids encoding desired polypeptides.

Abstract: DNA encoding the gene for the synthetase enzyme capable of generating &dgr; (L-a-aminoadipyl)-L-crysteinyl-D-valine (ACV) from its constituent amino acids was obtained from several penicillin and cephalosporin producing organisms, e.g. Penicillium chrysogenum, cephalosporium and a Flavobacterium species. The DNA was used to prepare recombinant vectors comprising the ACV synthetase gene and hosts transformed with such vectors. The ACV synthetase gene can form part of a gene cluster comprising other genes involved in -&bgr;-lactam biosynthesis and the production of penicillin by expression of the entire biosynthetic gene cluster for the synthesis of penicillin from primary amino acids is described. Suitable hosts in which expression can take place include heterologous hosts which are naturally non-producers of penicillin.

Abstract: Provided is a novel &bgr;-glucosidase from Orpinomyces sp. PC2, nucleotide sequences encoding the mature protein and the precursor protein, and methods for recombinant production of this &bgr;-glucosidase.

Abstract: The present invention relates to the biosynthesis of &bgr;-lactam antibiotics. More specifically, the invention relates to processes of producing &bgr;-lactam antibiotics in vivo and in vitro. Also contemplated is a novel enzyme capable of catalyzing certain steps involved in &bgr;-lactam biosynthesis. Further, the invention relates to a DNA construct encoding the novel enzyme, a recombinant vector or transformation vehicle comprising the DNA construct, and finally a cell comprising the DNA construct or recombinant vector.

Abstract: DNA encoding triol polyketide synthase (TPKS) has been isolated, purified and sequenced. Expression vectors comprising TPKS, cells transformed with the expression vectors, and processes employing the transformed cells are provided.