Abstract: A novel gene conferring resistance to spiramycin in Streptomyces and related organisms was cloned from a genomic library of Streptomyces ambofaciens DNA. A thirty-one Kb fragment of S. ambofaciens DNA including the spiramycin-resistance gene was isolated from this library on a cosmid designated pKC592. The novel spiramycin-resistance gene can be isolated on an .about.2.9 Kb BamHI fragment by subcloning restriction fragments obtained from the pKC592 insert DNA. This BamHI fragment contains all of the information required for the expression of the spiramycin resistant phenotype in Streptomyces. Vectors and transformants containing the novel spiramycin resistance gene are provided.

Abstract: An improved process for producing A-21978C cyclic peptide derivatives having a C.sub.2 -C.sub.14 alkanoyl side chain which comprises feeding a C.sub.2 -C.sub.14 alkanoic acid, or an ester or salt thereof, to the A-21978C-producing culture during the production stages of the fermentation.

Abstract: The compound 3,7-dihydroxytropolone having the formula ##STR1## is produced by fermentation of Streptomyces tropolofaciens and is found to inhibit the growth of mammalian tumors.

Abstract: Improved fermentation process for producing the Gram-positive antibiotic A47934 which comprises cultivating a new strain of Streptomyces toyocaensis, NRRL 18112, and a biologically purified culture of this microorganism are provided.

Abstract: The plasmid pSG5 which, because of its molecular length of about 12.7 kb and its four unique restriction sites, can be used for the construction of plasmid vectors for Streptomycetes, for example of shuttle vectors between Streptomycetes and other microorganisms, can be isolated from a culture of Streptomyces ghanaensis DSM 2932.

Abstract: The tlrB gene is a novel tylosin resistance-conferring gene isolated from Streptomyces fradiae and used to construct a number of cloning vectors for use in Streptomyces and related organisms. One such cloning vector, plasmid pSVB9, can be obtained in S. lividans under the accession number NRRL 18073. S. lividans is the preferred host when the tlrB gene is used to select tylosin-resistant Streptomyces transformants.

Abstract: DNA cloning shuttle vectors, including a cosmid shuttle vector, for E. coli and Streptomyces are disclosed. Specifically, disclosed shuttle vectors pAL7002 (NRRL B-18055) and pNJl (NRRL B-18054) contain an E. coli origin of replication, Streptomyces replication functions, and antibiotic resistance markers for both E. coli and Streptomyces. In addition, pNJl contains a cos sequence. Novel 2-norerythromycin antibiotics A, B, C, and D, which were produced in a strain Streptomyces erythreus 12693-240 (NRRL B-18053) transformed by pNJl bearing DNA from Streptomyces antibioticus, are also disclosed. The present invention also provides a method for producing novel antibiotics. This method for antibiotic production is applied to the transformation of a blocked mutant of S. erythreus with genomic DNA from S. antibioticus but may be more broadly applied to genes to antibiotic-producing strains transformed into cells which are blocked in the pathway for production of a different antibiotic.

Abstract: A process for purifying lysocellin which comprises mixing lysocellin solids with sufficient halogen acid to convert fatty acid ester salt impurities into water-soluble metal halogen salts and water-insoluble free fatty acids and to convert lysocellin salts into water-soluble metal halogen salts and water-insoluble lysocellin acid, separating the halogen salts from the lysocellin acid and fatty acid solids, mixing the lysocellin acid and fatty acid solids with sufficient caustic reagent to convert free fatty acids into water-soluble alkali metal salts and to convert lysocellin acid into a water-insoluble alkali metal lysocellin salts, and separating the water-soluble fatty acid alkali metal salts from the alkali metal lysocellin solids.

Abstract: A process for producing unnatural penicillins and cephalosporin derivatives thereof in which peptide analogs of ACV in which the L-.alpha.-aminodipyl moiety is replaced by L-S-carboxymethyl cysteine or other obvious substituents, are reacted with cyclase, epimerase, ring expansion and hydroxylase enzymes isolated from a cell free extract of a prokaryotic organism such as S. clavuligerus. The product depends upon the presence or absence of co-factors such as ferrous ion, .alpha.-ketoglutarate, and ascorbate. In an alternative embodiment, a penicillin analog having the formula: ##STR1## may be reduced with L-cysteine to produce an analog of isopenicillin N which may be reacted with the enzyme reagent to produce the desired penicillin or cephalosporin.

Abstract: A novel method of selecting Streptomyces recombinant DNA-containing host cells and vectors useful in exemplifying the method are described. The vectors confer apramycin resistance to sensitive Streptomyces host cells and thus provide a convenient method of selecting Streptomyces transformants. The apramycin resistance-conferring gene used in the method is an acetyltransferase aac(3)IV gene and can be isolated from E. coli K12 BE1041/pKC309 (NRRL B-15827) on an .about.1.5 kb PstI-EcoRI restriction fragment.

Abstract: The compound 3,7-dihydroxytropolone having the formula ##STR1## is produced by fermentation of Streptomyces tropolofaciens and is found to inhibit the growth of mammalian tumors.

Abstract: A new strain of Streptomyces pactum, NRRL 15970, and an improved fermentation process for producing the polyether antibiotic A80438 using this microorganism are provided.

Abstract: The strain Streptomyces coelicolor DSM 3030 excretes into the fermentation medium high yields of a bacteriolytic enzyme product which is very active against Gram-positive and Gram-negative bacteria. Preferred fermentation media contain sugar beet molasses and/or calcium ions.

Abstract: Improved fermentation process for producing the gram-positive A-21978C antibiotics which comprises cultivating a new strain of Streptomyces roseosporus, NRRL 15998, and the biologically purified culture of this microorganism are provided.

Abstract: A microbial process for converting codeine to 14-hydroxycodeine is provided. This process comprises aerobically culturing codeine with bacteria of the genus Streptomyces for at least about 3 days in a rich medium such as soybean flour medium.

Abstract: A novel complex designated herein as rigolettone complex is produced by fermentation of Streptomyces aburaviensis strain C-38,242 (ATCC 39290). The complex and its purified bioactive components, jildamycin and mantuamycin, exhibit antitumor activity in mouse tumor systems.

Abstract: The present invention comprises novel DNA compounds which encode human protein C activity. A variety of eukaryotic and prokaryotic recombinant DNA expression vectors have been constructed that comprise the novel protein C activity-encoding DNA and drive expression of protein C activity when transformed into an appropriate host cell. The novel expression vectors can be used to produce protein C derivatives, such as non-carboxylated, non-glycosylated, or non-hydroxylated protein C, and to produce protein C precursors, such as nascent or zymogen protein C, and to produce sub-fragments of protein C, such as active or inactive light and heavy chain. The recombinant-produced protein C activity is useful in the treatment and prevention of a variety of vascular disorders.

Abstract: A method of inactivating cytosolic aspartate aminotransferase isozyme comprises addition of a specific inhibitory enzyme.A method for the fractional determination of aspartate aminotransferase isozyme activities, which comprises (a) inactivating the cytosolic aspartate aminotransferase isozyme in a reaction mixture containing the specimen by the addition of a specific inhibitory enzyme, followed by determination of the residual mitochondrial aspartate aminotransferase isozyme activity, and (b) determination of the cytosolic isozyme activity by subtracting the activity of mitochondrial isozyme determined in (a) from the total activity of aspartate aminotransferase isozymes.A cytosolic aspartate aminotransferase isozyme inhibiting composition contains an effective cytosolic aspartate aminotransferase isozyme inhibitory amount of a specific inhibitory enzyme.

Abstract: The invention relates to a method and cloning vehicle for the expression of a functional polypeptide in Streptomyces. A recombinant DNA cloning vehicle was genetically engineered to bring the expression of the neomycin phosphotransferase gene under the control of the Escherichia coli bacteriophage .lambda.p.sub.L promoter.

Abstract: A method for transforming Cephalosporium and other lower eukaryotes is disclosed. The method involves inserting a recombinant DNA cloning vector comprising a Saccharomyces cerevisiae transcriptional and translational activating sequence positioned for expression of hygromycin phosphotransferase into a host cell and then growing the host cell under selective conditions. The vectors optionally further comprise Cephalosporium ribosomal DNA and also sequences that allow for replication and selection in E. coli and Streptomyces.

Abstract: The present invention discloses selectable, recombinant DNA shuttle vectors for use in streptomycetes and E. coli. The shuttle vectors of the present invention are present at moderately high copy number. The invention further discloses transformants of the aforementioned vectors.

Abstract: A novel method of selecting Streptomyces recombinant DNA-containing host cells and vectors useful in the method are described. The vectors confer spiramycin resistance to sensitive Streptomyces host cells and thus provide a convenient method of selecting Streptomyces transformants. The novel spiramycin resistance-conferring gene described can be isolated on an .about.3.8 kb Bc1I restriction fragment from plasmid pNAS105. Plasmid pNAS105 can be isolated from Streptomyces griseofuscus C581/pNAS105 (NRRL 15919).

Abstract: The present invention is a method for expressing functional polypeptides in Streptomyces using a recombinant DNA expression vector comprising a novel transcriptional- and translational- activating sequence. The novel activating sequence can be synthesized by conventional methods and used in Streptomyces expression vectors. One such vector, plasmid pFJ350, expresses and confers hygromycin resistance in Streptomyces host cells.

Abstract: It has been discovered that rubradirin can be used to treat rubradirin-sensitive, methicillin-resistant staphylococcal infections.

Abstract: A new method is provided for forming crystals of amphotericin B directly in fermentation broth which crystals are easily separable without use of costly solvent extraction techniques which method includes a direct microbial cell autolysis step to induce crystal formation.

Abstract: L-aminoacylases S.sub.1 and S.sub.2 derived from actinomycetes and having physicochemical characteristics such that it is a L-aminoacylase which acts on a N-acyl-L-amino acid to give a L-amino acid, its substrate profile is wide, and it acts not only on a N-acyl derivative of a natural L-amino acid, but also on a N-acyl derivative of a synthetic L-amino acid, while it does not act on a N-acyl-D-amino acid, a DL-N-acetyl-.alpha.methylbenzylamine and a N-acetyl-D-glucosamine, etc.

Abstract: Cloning vectors are disclosed to obtain secretion of a desired protein from a host Streptomyces when a structural gene coding for the protein is inserted into the vector. The vector has: (1) regulatory DNA that includes a promoter sequence effective to start transcription in the host Streptomyces and DNA that encodes a ribosome-binding site; (2) a DNA sequence that codes for a signal sequence that occurs naturally in a Streptomyces strain or that derives from such a DNA sequence; and (3) at least one engineered restriction endonuclease recognition site positioned for the insertion of a structural gene, the DNA that encodes a signal sequence and attached structural gene being transcribed and translated together under the control of the regulatory DNA. Expression vectors are disclosed which include a structural gene coding for a desired protein so positioned. Streptomyces cells containing the vector and methods of using them to produce the desired protein are disclosed.

Abstract: The present invention provides a hydrogen peroxide-forming sarcosine oxidase, wherein it is obtainable from Streptomycetaceae and at 25.degree. C. in 0.15 mol/liter potassium phosphate (pH 7.9), in the presence of surface-active substances, still shows after 2 days an activity of at least 40% of the initial activity.

Abstract: A biologically pure culture of Streptomyces sandaensis which is capable of producing an antitumor and antimicrobial compound, designated FR-900482 substance, is disclosed.

Abstract: The present invention relates to the compound naphthomycin H of the formula I ##STR1## and to a microbiological process for its preparation. The compound is active against Gram-positive bacteria and fungi and can be used as an antibiotic.

Abstract: Acids, esters, imine acids, imine esters, and imine amides derived from 6-formyl-4,7,9-trihydroxy-1-phenazinecarboxylic acid, methyl ester and from 6-formyl-4,7,9-trihydroxy-8-methyl-1-phenazinecarboxylic acid, methyl ester demonstrate anti-microbial and antineoplastic activity.A purified strain of Streptomyces galanosa, NRRL 15738, is capable of producing 6-formyl-4,7,9-trihydroxy-8-methyl-1-phenazinecarboxylic acid, methyl ester in isolable quantities from a fermentation broth containing assimilable sources of carbon and nitrogen.

Abstract: A process for preparing an enzyme capable of inactivating cytosolic aspartate aminotransferase isozyme. The process comprises cultivating a strain of Streptomyces violaceochromogenes species capable of producing said enzyme to produce and accumulate said enzyme and recovering said enzyme from the culture.

Abstract: A process for the production of aminoglycoside antibiotics using fused protoplasts derived from streptomyces. The cells are precultured in a medium containing sucrose, calcium and magnesium salts. Protoplasts are formed and then fused. The fused protoplasts are regenerate and antibiotic producing ability is screened for. The regenerate cells produced an antibiotic complex of modified composition or demonstrated increased or reduced antibiotic productivity compared to the fusion partners.

Abstract: The invention relates to a method for controlling stem break in cereal plants, wherein the fungus Pseudocercosporella anguioides or Pseudocercosporella aestiva is applied to the cereal plants their seed or their area of cultivation.

Abstract: A DNA fragment from Streptomyces sp. which contains a gene which can code for an excretable protein is isolated, inserted into a plamid vector and used to transform other Streptomycetes.

Abstract: Antibiotic A41030, a complex of 7 individual factors, is produced by submerged, aerobic fermentation of new Streptomyces virginiae NRRL 12525, and Streptomyces virginiae NRRL 15156. The antibiotic factors are separated and possess antibacterial activity against Staphylococcus and Streptococcus species which are penicillin resistant. In addition, the antibiotic factors have shown inhibition of Streptococcus pneumonia Park I. The complex and the individual factors enhance feed efficiency in ruminant animals, and are growth promoters in chickens and swine, and are especially valuable in milk production in dairy cattle.

Abstract: A method of cloning endogenously modified Streptomycetes DNA, which is normally rejected by restrictionless heterospecific hosts, is disclosed. The method uses bacteriophage lambda to construct a genomic library of modified Streptomycetes DNA; such lambda-containing Streptomycetes DNA is replicated to provide a source of non-modified Streptomycetes DNA. This non-modified DNA is subcloned into a selectable cloning vector and used to transform restrictionless hetero-specific hosts. The transformants can then be screened for clones containing genes of interest.

Abstract: Novel plasmid pVE1, deletion mutants thereof, recombinant derivatives thereof, which is the same as the genome or nucleic acid of such plasmids and derivatives of such genome, which are useful as recombinant DNA cloning vectors into host organisms, such as bacteria, for example, Streptomyces avermitilis; portions of such plasmid genome are additionally useful as adjuncts in recombinant DNA cloning procedures, for examples: 1. to permit the maintenance of cloned DNA in the host, either in an integrated state or as an autonomous element; 2. to serve as promoters for increasing expression of endogenous or foreign genes wherein said promoters are ligated to such genes or otherwise serve as promoters; and 3.

Abstract: N-acyl-DL-3-(3,4-dihydroxyphenyl)serine or a catecholic hydroxyl-protected derivative thereof is stereospecifically de-acylated by reaction with a microorganism of the genus Streptomyces or Streptoverticillium having an acylase or with an extract of said microorganism containing said acylase, to produce L-3-(3,4-dihydroxyphenyl)serine or the hydroxyl-protected derivative thereof, with the N-acyl-D-3-(3,4-dihydroxyphenyl)serine compound remaining unaltered. The L-3-(3,4-dihydroxyphenyl)serine compound so produced can be separated from the N-acyl-D-3-(3,4-dihydroxyphenyl)serine compound owing to the difference in the properties of them.

Abstract: The present invention disclosed novel recombinant DNA cloning vectors including pMND1000 and vectors derived therefrom for use in Streptomyces and related organisms. These novel cloning vectors contain genetic markers that provide antibiotic resistance or colorimetric selectivity to the host cells. The invention further comprises transformants of the aforementioned vectors.

Abstract: A hitherto undescribed microorganism, Streptomyces virginiae NRRL 12525, which upon culturing produces the A41030 antibiotic complex comprising several factors. The A41030 antibiotics produced show antibacterial activity against the gram-positive genera Staphylococcus and Streptococcus which are resistant to penicillin. In addition, these antibiotic act to promote growth and improve feed efficiency in ruminant animals, poultry and swine, and other livestock, and to improve milk production in ruminant animals.

Abstract: Enzymes extracted from a prokaryotic .beta.-lactam producing microorganism are immobilized on a support for producing desacetoxycephalosporin and analogs thereof from L-.alpha.-aminoadipyl-L-cysteinyl-D-valine and analogs thereof. The enzymes are an epimerase, a cyclase and a ring expansion enzyme extracted preferably from S. clavuligerus, S. cattleya or S. lipmanii. The support is preferably a diethylaminoethyl ion exchange resin.

Abstract: Novel antibiotic U-68,204 is produced in a fermentation under controlled conditions using a biologically pure culture of the microorganism Streptomyces thiolactonus, NRRL 15439. This antibiotic is active against various Gram-positive bacteria. Thus, antibiotic U-68,204 can be used in various environments to eradicate or control such bacteria.

Abstract: Xylose isomerase, from strains of the Streptomyces murinus cluster, a method for production of such xylose isomerase, immobilized xylose isomerase and a method for isomerization of glucose to fructose therewith.

Abstract: A microorganism of a new species of the genus Streptomyces having an ability to produce chitinase has been found, and a method of producing chitinase using this microorganism is disclosed.

Abstract: The present invention disclosed novel recombinant DNA cloning vectors for use in Streptomyces and related organisms. These novel cloning vectors contain genetic markers that provide antibiotic resistance or colorimetric selectivity to the host cells. The invention further comprises transformants of the aforementioned vectors.

Abstract: A novel method of selecting Streptomyces recombinant DNA-containing host cells and vectors useful in the method are described. The vectors confer tylosin resistance to sensitive Streptomyces host cells and thus provide a convenient method of selecting Streptomyces transformants. The novel tylosin resistance-conferring gene described can be isolated on an .about.2.6 kb KpnI restriction fragment from plasmid pSVB2. Plasmid pSVB2 can be isolated from Streptomyces lividans TK23/pSVB2 (NRRL 15880).

Abstract: This invention relates to new polypeptide antibiotics designated LL-BO2964.alpha., LL-BO2964.beta., LL-BO2964.gamma., and a mixture thereof designated LL-BO2964, produced during microbiological fermentation, under controlled conditions, using a new strain of Streptomyces coeruleorubidus subspecies rubidus or a mutant thereof. The new antibiotics are active against a variety of microorganisms and are also useful in treating tuberculosis.

Abstract: A process for producing mitomycin A by fermentation, which involves culturing a microorganism belonging to the genus Streptomyces, which is capable of producing mitomycin A and having at least one property of (1) deficiency in an ability to produce mitomycin C and (2) a resistance to tryptophan analog, in a culture medium forming and accummulating mitomycin A in the culture medium; and recovering mitomycin A therefrom. The microorganism preferably involves Streptomyces caespitosus T-17-135 (NRRL 12508) or Streptomyces caespitosus (NRRL 12513).

Abstract: The plasmid p SVH 1, which is obtained from Streptomyces venezuelae DSM 40755 and which has a molecular weight of 8.4 megadaltons, a contour length of 4.1 .mu.m and a molecular size of 12.6 kilobases, and its use for the construction of a vector and for cloning foreign DNA in suitable host organisms.