Abstract: Compounds of Structural Formula (I) ##STR1## are produced by directed biosynthesis. These compounds are squalene synthetase inhibitors useful as cholesterol-lowering agents.

Abstract: Incubation of 13.beta.-hydroxy ivermectin aglycone with a species of Bacillus subtilis or the incubation of 13-deoxy ivermectin aglycone with a mixed culture of a species of Bacillus subtilis and of Streptomyces griseus results in the production of 13-.beta. ivermectin monoglucopyranoside as the major product and of 5-.beta. ivermectin monoglucopyranoside as the minor product.

Abstract: Novel cytochalasins are the biotransformed products after incubation with a substrate in a culture of the microorganism Kibdelosporangium sp. (Merck Culture Collection MA 6559), ATCC No. 53771. The compounds of the present invention inhibit HIV protease and are useful in the prevention or treatment of infection by HIV and the treatment of AIDS, either as a compound, pharmaceutically acceptable salt, pharmaceutical composition ingredient, whether or not as a prodrug or as a combination with other antivirals, anti-infectives, immunomodulators, antibiotics or vaccines.

Abstract: This invention relates to strains of the species Curvularia lunata isolated from tree bark and useful in a fermentation process to form compounds of formula (I): ##STR1##

Abstract: New polyether antibiotic A80789, its acyl ester, alkyl ester, and alkyl ether derivatives, and salts thereof, are useful as antibacterial and anticoccidial agents and increase feed-utilization efficiency in animals. Methods of making A80789 by culture of Streptomyces hygroscopicus NRRL 18513, and combinations of the A80789 compounds with nicarbazin, 4,4'-dinitrocarbanilide, certain napthalenamine and benzenamine compounds and are also provided.

Abstract: A method for producing streptovaricin by culturing a streptovaricin producing strain in the presence of a nonionic adsorbent. This procedure substantially increases the production efficiency of the streptovaricin. A second embodiment wherein the streptovaricin producing strain is produced in the presence of fumaric acid or its water soluble salts to provide improvements in production efficiency is also disclosed.

Abstract: Mutants of Streptomyces avermitilis lacking ability to produce glycosylated avermectins and lacking branched-chain 2-oxo acid dehydrogenase activity, method for preparation thereof, and use thereof to produce natural and non-natural avermectin aglycones useful as parasiticides.

Abstract: Aranorosinol-A and Aranorosinol-B are compounds of the formula ##STR1## in which R is H (Aranorosinol-A) or CH.sub.2 COCH.sub.3 (Aranorosinol-B); said compounds have antibacterial and antifungal activity.

Abstract: Streptomyces avermitilis lacking branched-chain amino acid transaminase activity and/or branched-chain 2-oxo acid dehydrogenase activity, methods for preparation thereof, and use thereof to produce natural and non-natural avermectins useful as parasiticides.

Abstract: A microbiological process for the oxidation of methyl groups in aromatic 5- or 6-member ring heterocycles to the corresponding carboxylic acid. The heterocycle serves as the substrate and exhibits no substituent on the carbon atoms adjacent to the methyl groups to be oxidized. The reaction of the heterocycle takes place by means of microorganisms of the genus Pseudomonas utilizing toluene, xylene, or cymene. The enzymes of the microorganisms been previously induced.

Abstract: Streptomyces avermitilis lacking branched-chain 2-oxo acid dehydrogenase activity and avermectin B O-methyltransferase activity, method for preparation thereof, and use thereof to produce natural and non-natural B avermectins useful as parasiticides.

Abstract: A natamycin producing Streptomyces species ferments to produce natamycin. A spore suspension of the Streptomyces species is propagated in a predetermined medium to obtain a quantity of Streptomyces cells. The Streptomyces cells ferment in a predetermined production medium having a controlled pH to produce a recoverable amount of natamycin.

Abstract: The known compound, 13.beta.-13-deoxy-22,23-dihydro-avermectin -B1a/B1b Aglycone is prepared microbiologically from cultures of the novel microorganisms (MA-6762, ATCC 55069, MA-6763 ATCC 55070) or the known microorganism Streptomyces lavendulae MA-6555 (ATCC 14159 or ATCC 55330). The compound is prepared by the biotransformation of 13-deoxy-22,23-dihydro avermectin B1a/B1b aglycone which oxidizes the 13-position and epimerizes the 13-position hydroxy group.

Abstract: This disclosure describes novel antibacterial agents designated LL-E10985.alpha., LL-E19085.beta., LL-E19085.gamma., LL-E19085.zeta. and LL-E19085.eta., having the structure: ##STR1## their production by aerobic fermentation of a new subspecies of Micromonospora citrea NRRL 18351 and mutants thereof, and the isolation and purification thereof.

Abstract: Chemical reactions capable of being rate-enhanced by auxiliary species which interact with the reactants but do not become chemically bound to them in the formation of the final product are performed in the presence of antibodies which promote the reactions. The antibodies contain regions within their antigen binding sites which recognize the auxiliary species in a conformation which promotes the reaction. The antigen binding site frequently recognizes a particular transition state complex or other high energy complex along the reaction coordinate, thereby promoting the progress of the reaction along the desired route as opposed to other less favorable routes. Various classes of reaction together with appropriate antigen binding site specificities tailored for each are disclosed.

Abstract: Fermentation of the microorganism Streptomyces sp. MA6751 (ATCC No. 55043) in the presence of the Angiotensin II (A II) receptor antagonist ##STR1## yields an N2-glucuronide analog which is also an A II antagonist useful in the treatment of hypertension and congestive heart failure and other indications known to respond to A II antagonists.

Abstract: A novel antitumor substance BE-13793C or a pharmaceutically acceptable salt thereof, which is represented by the following formula: ##STR1## an anticancer agent comprising the novel substance or a pharmaceutically acceptable salt thereof, a method of producing the novel substance and a microorganism capable of producing the novel substance are disclosed.

Abstract: A microbiological process for oxidation of methyl groups in aromatic 5- or 6-ring heterocycles to the corresponding carboxylic acid. The reaction of the heterocycle takes place by microorganisms of the genus Pseudomonas, which utilize toluene, xylene or cymene. An inducer, the aromatic heterocycle, as the substrate, and a carbon source and energy source are fed in and, after the maximal product concentration is reached, the product is separated.

Abstract: Disclosed is a method for selecting a mutant strain belonging to the genus Streptomyces which is a hyper-producer of Streptovaricin C superior to those know heretofore. This is accomplished by first subjecting a natural strain of Streptomyces spectabilis to conditions so as to isolate organisms which are streptovaricin resistant. The streptovaricin resistant organisms thus isolated are then subjected to mutagenesis and then cultured. The colonies which are asporogenous are individually cultured in fermentation batches such that the strains take the form of pellets of varying sizes and colors. From the batch having the most heterogeneous mixture of pellets, the smallest pellet or the pellet(s) having the deepest color (usually deep red or crimson) is isolated. We have discovered that the strain of this pellet has a high likelihood of being a hyperproducer of streptovaricin. The strain of this pellet may then be subjected to fermentation conditions to produce streptovaricin.

Abstract: Described is a new process for selectively acylating FK-506 type immunosuppressant macrolides, including immunomycin (FK-520), in the C-32 position, under novel conditions utilizing an immobilized lipase enzyme, an acyl donor, and a dry, non hydroxylic organic solvent. The enzyme is absorbed onto a solid support and the enzyme/support catalyzes the C-32 acylation. The enzyme/support complex can then be filtered from the reaction mixture and, recycled for use.

Abstract: Disclosed is a method for selecting a mutant strain belonging to the genus Streptomyces which is a hyper-producer of Streptovaricin C superior to those know heretofore. This is accomplished by first subjecting a natural strain of Streptomyces spectabilis to conditions so as to isolate organisms which are streptovaricin resistant. The streptovaricin resistant organisms thus isolated are then subjected to mutagenesis and then cultured. The colonies which are asporogenous are individually cultured in fermentation batches such that the strains take the form of pellets of varying sizes and colors. From the batch having the most heterogeneous mixture of pellets, the smallest pellet or the pellet(s) having the deepest color (usually deep red or crimson) is isolated. We have discovered that the strain of this pellet has a high likelihood of being a hyperproducer of streptovaricin. The strain of this pellet may then be subjected to fermentation conditions to produce streptovaricin.

Abstract: Molecules that catalyze the reaction of a cyclic conjugated diene having a fugitive leaving group in a five- or six-membered ring containing the conjugated double bonds and a dienophile that contains a reactive multiple bond to form a reaction product that contains a five- or six-membered ring and at least two endocyclic double bonds from a Diels-Alder [4+2] cycloaddition/fragmentation reaction that is followed by a reverse Diels-Alder reaction are disclosed. The catalyst molecules contain an antibody combining site that immunoreacts with an antigen whose structure (i) includes a [2.2.1] or [2.2.2] bicyclic ring system that is absent from the reaction product and (ii) contains at least one endocyclic double bond fewer than the number of endocyclic double bonds present in the reaction product. Methods of preparing and using the catalyst molecules are also disclosed.

Abstract: A microorganism for selective production of a specific compound of avermectin having one or more of the following properties:specific accumulation of avermectin compound "a",effective incorporation of isoleucine or its keto acid (3-methyl-2-oxovaleric acid) into avermectin molecule, andmarkedly suppressed incorporation of valine or its keto acid (2-oxoisovaleric acid) into avermectin molecule.

Abstract: An acidic polycyclic ether antibiotic, having structure established by X-ray crystallography, is formed by fermentation of a novel microorganism, Streptomyces hygroscopicus ATCC 53626. This novel antibiotic is useful as an anticoccidial in chickens and as a growth promotant in cattle and swine.

Abstract: Disclosed is a process for preparing 2-halogeno-3-hydroxy-3-phenylpropionic acid ester compounds represented by the formula (I): ##STR1## wherein Ring A is a phenyl group which may be substituted, R.sup.1 is an ester residue, and X is a halogen atom, which comprises permitting an enzyme having the ability of stereoselectively reducing oxo group to hydroxy group to act on 2-halogeno-3-oxo-3-phenylpropionic acid ester compounds represented by the formula (II): ##STR2## wherein Ring A, R.sup.1 and X have the same meanings as defined above.

Abstract: This invention relates to strains of the species Curvularia lunata isolated from tree bark and useful in a fermentation process to form compounds of formula (I): ##STR1##

Abstract: A process for the preparation of "natural" methyl anthranilate which comprises the microbial N-demethylation of methyl N-methyl-anthranilate is disclosed.

Abstract: An antibiotic agent produced by the cultivation of Zalerion arboricola which is a cyclic lipopeptide with very high activity against human pathogens and of very low mammalian toxicity is described. Its production and isolation are also described.

Abstract: Fermentation of the microoganism Actinoplanacete sp. in the presence of the angiotensin II receptor antagonist, 5,7-dimethyl-2-ethyl-3-((2'-tetrazol-5-yl)biphenyl-4-yl)methyl-3H-imidazo[ 4,5-b]pyridine, compound III, ##STR1## yields 2-ethyl-5-hydroxymethyl-7-methyl-3-((2'-tetrazol-5-yl)biphenyl-4-yl)methyl -3H-imidazo[4,5-b]pyridine, compound I, and 2-ethyl-7-hydroxymethyl-5-methyl-3-(2'-tetrazol-3-((2'-tetrazol-5-yl)biphe nyl-4-yl)methy-3H-imidazo[4,5-b]pyridine, compound II, ##STR2## both of which are angiotensin II receptor antagonists useful in the treatment of hypertension and congestive heart failure and other indications known to respond to angiotensin II antagonists.

Abstract: A method for separation and recovery of polymeric beads from an antibiotic fermentation broth comprising suspending a mixture of the beads and any inherent mold from the fermentation in an aqueous solution having a specific gravity which is effective to cause the beads to form a discrete layer at or on the surface of the solution, separate and apart from the mold. The separate layer of the beads may then be easily removed from the liquid by a conventional physical methods.

Abstract: The present invention relates to a one-step microbial process for the preparation of 13.beta.-hydroxy- or 14,15-epoxy-milbemycins of the following formulae I and II ##STR1## in which R.sub.1 and R.sub.1 ' represent methyl, ethyl, isopropyl or sec.-butyl or represent the group ##STR2## in which X represents methyl, ethyl or isopropyl, and A and A' represent the group ##STR3## in which R.sub.2 represents hydrogen, --C(O)-CH.sub.2 O-C(O)-CH.sub.2 CH.sub.2 -COOH or --C(O)-CH.sub.2 CH.sub.2 -COOH, or mixtures of compounds of the formulae I and II, which process comprises bringing a milbemycin of the formula III ##STR4## dissolved in a liquid phase, in which R.sub.3 represents R.sub.1 or R.sub.1 ' and R.sub.4 represents A or A', and R.sub.1, R.sub.1 ', A and A' have the meanings given for formulae I and II, into contact with a microorganism that is capable of 13.beta.-hydroxylation or 14,15-epoxidation or of both reactions, or into contact with active constituents thereof.

Abstract: Compounds as described having the partial formula ##STR1## These compounds may have a 5-OH or --OMe group and at the 25- position an isopropylene group substituted by methyl, ethyl or isopropyl.The compounds may be used in agriculture or medicine as antiparasitics, and may be prepared by culturing certain Streptomyces strains, in particular Streptomyces thermoarchaensis NC1B 12015.

Abstract: The present invention relates to a method for quantitatively assaying the presence of DSP toxins such as okadaic acid and dinophysistoxin-1 in marine samples. The method comprises the steps of preparing a marine extract, fractionating the prepared marine extract and selecting the extract fraction containing the toxin to be assayed. Once the desired extract fraction has been selected, a labelled substrate for protein phosphatase and at least one protein phosphatase are added to the extract in an assay. The amount of toxin present is quantitatively measured by the ability of the extract fraction to inhibit catalysis, mainly dephosphorylation, of the labelled substrate by protein phosphatases, such as phosphatase-1 (PP1) or phosphatase-2A (PP2A). Preferably, the method of the present invention is used to assay the presence of okadaic acid in marine organisms such as mussels, oysters, scallops, phytoplankton and the like.

Abstract: A method for purification of mitomycin C comprises;a. a step of treating the culture of a mitomycin C-producing microorganism with reverse phase adsorption resin to adsorb mitomycin C onto the resin;b. a step of eluting mitomycin C with ethyl acetate out of the resin;c. a step of adding phosphate buffer to the eluate and then evaporating ethyl acetate;d. a step of passing, under pressure, the residue remaining after the evaporation through a column packed with a reverse phase adsorbent having a small particle diameter to adsorb mitomycin C onto the resin;e. a step of eluting mitomycin C with aqueous methanol out of the resin under pressure;f. a step of treating the eluate with a reverse phase adsorption resin to adsorb mitomycin C onto the resin;g. a step of eluting mitomycin C with methanol out of the resin; and,h. a step of concentrating the methanol eluate to crystallize mitomycin C.By this method, mitomycin C can be efficiently purified in an industrial scale.

Abstract: A mutant strain having a glucose consumption rate is at most 1/4 that of wild type strains is provided. The mutant strain belongs to Escherichia, Bacillus, Pseudomonas, or Serratia; has a glucose consumption rate of at most one fourth that of the corresponding wild type strain, and the feedback repression by biotin is removed. Further, a process for producing biotins using this mutant strain is provided.

Abstract: A method for selecting hyper-producing strains of streptovaricin C by culturing streptomyces spectabilis and separating the asporogenous colonies. The asporogenous colonies are then separately cultured and tested for streptovaricin productivity. Those colonies having the highest productivity may then be easily selected.

Abstract: This invention relates to new agents designated LL-F28249.alpha., LL-F28249.beta., LL-F28249.gamma., LL-F28249.delta., LL-F28249.epsilon., LL-F28249.zeta., LL-F28249.eta., LL-F28249.theta., LL-F28249.iota., LL-F28249.kappa., LL-F28249.lambda., LL-F28249.mu., LL-F28249.nu., and LL-F2924.omega., to their production by fermentation, to methods for their recovery and concentration from crude solutions, to processes for their purification and to pharmaceutically and pharmacologically-acceptable salts thereof. The present invention includes within its scope the biologically pure culture which produces there agents, derived from a newly-discovered and previously uncultured microorganism, Streptomyces cyaneogriseus subsp. noncyanogenus, NRRL 15773.

Abstract: There are disclosed new compound with significant antiparasitic activity which are prepared by fermenting the compounds paraherquamide or dihydroparaherquamide in a novel microorganism identified as Cunninghamella blakesleeana MF-4415. The compounds are best realized in the following structural formulae: ##STR1## wherein A is either a single or a double bond. The paraherquamide compound is modified by the microorganism by ring hydroxylation or ketonization. The compounds are significant antiparasitic and anthelmintic agents and compositions for that use are also disclosed.

Abstract: Method using tetra-aryl porphyrins for and, in particular, 5,10,15,20-tetrakis(4-carboxyphenyl)porphine as a fluorescent tracer for cancers of the lung, and as a radiotracer therefor as a complex with .sup.67 Cu. The latter complex also provides a source of beta radiation for selective destruction of lung malignancies as well as gamma radiation useful for image analysis of the situs thereof by single photon emission computed tomography, as an example, both in vivo. Copper-64 may be substituted for the .sup.67 Cu if only radiotracer characteristics are of interest. This lighter isotope of copper is a positron emitter, and positron emission tomography techniques cna be used to locate the malignant tissue mass.

Abstract: The novel antitumor antibiotic designated herein as dynemicin C is produced by fermentation of Micromonospora chersina M956-1 mutant F1085 (ATCC-55077). Dynemicin C and its triacetate derivative possess antibacterial and antifungal activity and also inhibit the growth of mammalian tumors.

Abstract: A new antibiotic cyclic lipopeptide and a method of producing it are described. The agent has very high activity against human pathogens and is of very low mammalian toxicity.

Abstract: An acidic polycyclic ether antibiotic, having structure established by X-ray crystallography, is formed by fermentation of a novel microorganism, Streptomyces sp. ATCC 55028. This novel antibiotic is useful as an anticoccidial in chickens, in the prevention or treatment of swine dysentery, as a growth promotant in cattle and swine, and as an anthelmintic in mammals, particularly in dogs, cats, sheep, cattle and swine.

Abstract: A method for selecting hyper-producing strains of streptovaricin C by culturing Streptomyces spectabilis and separating the asporogenous colonies. The asporogenous colonies are then separately cultured and tested for streptovaricin productivity. Those colonies having the highest productivity may then be easily selected.

Abstract: A novel mutant strain of Morel mushroom has been found to produce the blue pigment indigo by submerged nutrient culture medium containing a carbon and a fermentation in a nitrogen substrate. A red/purple pigment is also produced. The novel strain is Morchella rotunda nov. ES-1 sp. ATCC 20951.

Abstract: Fermentation of the microorganism Streptomyces sp. MA6744 (ATCC No. 55041) in the presence of the Angiotensin II (A II) receptor antagonist ##STR1## yields a 7-hydroxymethyl, a 5,7-dihydroxymethyl, a 7-carboxy and a 1'-hydroxy-5-hydroxymethyl analog, all of which are also A II antagonists useful in the treatment of hypertension and congestive heart failure and other indications known to respond to A II antagonists.

Abstract: A compound having the formula (I): ##STR1## is described, together with salts thereof and an enzymatic process for converting such compounds into clavulanic acid.A process for the preparation of the compound of formula (I) and its salts is disclosed, together with intermediates for use therein. This process involves the use of a novel enzyme system to effect the desired cyclisation, which enzyme system is preferably derived from a micro-organism, in particular a species of Streptomyces.

Abstract: A method for producing streptovaricin by culturing a streptovaricin producing strain in the presence of a nonionic adsorbent. This procedure substantially increases the production efficiency of the streptovaricin. A second embodiment wherein the streptovaricin producing strain is produced in the presence of fumaric acid or its water soluble salts to provide improvements in production efficiency is also disclosed.

Abstract: Fermentation of S. erythraea produces the novel avermectin, 28-hydroxy ivermectin aglycone.

Abstract: There are disclosed new compounds with significant antiparasitic activity which are prepared by fermenting 13-epi-ivermectin aglycone in a novel microorganism identified as Streptomyces avermitilis MA-5542. The 13-epi-ivermectin aglycone compounds are modified by the microorganism by methylation at the 5-hydroxy position and the addition of an .alpha.-L-oleandrose at the 13-position hydroxy. The compounds are significant antiparasitic and anthelmintic agents and compositions for that use are also disclosed.

Abstract: A compound of the formula (I): ##STR1## wherein R.sup.1, R.sup.2, and R.sup.3 are --COOR.sup.4, --COOR.sup.5, and --COOR.sup.6, respectively; R.sup.4, R.sup.5, and R.sup.6 each is hydrogen, lower alkyl, or alkali metal; W is hydroxyl; X, Y, and Z each is hydrogen or hydroxyl; a dotted line indicates the presence or absence of a single bond; or where W/R.sup.3, X/R.sup.1, and/or Z/R.sup.3 may be combined together, a lactone is formed, which compound is useful as a phospholipase A.sub.2 inhibitor. Process for the production of the compound (I) and a cell culture of a microorganism Circinotrichum falcatisporum RF-641 producing the same are also provided.