Schering Corporation

Harbor Branch Oceanographic Institution, Inc.

Ann C Horan

Mahesh G Patel

Joseph A Marquez

Thomas J Hosted

Vincent P Gullo

Jay A Waitz

Tim X Wang

Min Chu

Vinod R Hegde

Stephen J Coval

Shirley A Pomponi

J Allan Waitz

Raymond Cooper

Ingrid-Agneta Gunnarsson

Frank A Gentile

Gerald H Wagman

James A Matson

Jerzy Golik

George H Miller

Imbi Truumees

Joseph Terracciano

Raymond F Yarborough

Shirley A Pompni

Ellen B Barrabee

Vinod R Hedge

Manohar G Kalyanpur

Arthur H King

Richard W Vaughan

This invention is directed to nucleic acids which encode the proteins that direct the synthesis of the orthosomycin everninomicin and to use of the nucleic acids and proteins to produce compounds exhibiting antibiotic activity based on the everninomycin structure. The DNA sequence for the gene clusters responsible for encoding everninomicin biosynthetic genes, which provide the machinery for producing everninomicin, are provided. Thus, this invention provides the nucleic acid sequences needed to synthesize novel everninomicin-related compounds based on everninomicin, arising from modifications of the DNA sequence designed to change glycosyl and modified orsellinic acid groups contained in everninomicin. Asite-specific integrase gene is also provided, which can be incorporated in a vector for integration into any actinomycete, and, particularly into. Thus, the invention further provides methods for introducing heterologous genes into an actinomycete chromosome using this particular vector.

Everninomicin biosynthetic genes

Everninomicin biosynthetic proteins

Plasmid genes fromvar.ATCC39149 pMLP1 have been isolated cloned, sequenced and functionally identified. These genes have been used to create vectors which integrate in a site-specific manner into the host chromosome of actinomycete species.

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This invention is directed to nucleic acids which encode the proteins that direct the synthesis of the orthosomycin everninomicin and to use of the nucleic acids and proteins to produce compounds exhibiting antibiotic activity based on the everninomycin structure. The DNA sequence for the gene clusters responsible for encoding everninomicin biosynthetic genes, which provide the machinery for producing everninomicin, are provided. Thus, this invention provides the nucleic acid sequences needed to synthesize novel everninomicin-related compounds based on everninomicin, arising from modifications of the DNA sequence designed to change glycosyl and modified orsellinic acid groups contained in everninomicin. A.site-specific integrase gene is also provided, which can be incorporated in a vector for integration into any actinomycete, and, particularly into. Thus, the invention further provides methods for introducing heterologous genes into an actinomycete chromosome using this particular vector.

Plasmid genes from pMR2 have been isolated, cloned, sequenced and functionally identified. These genes have been used to create vectors which can be used to express actinomycete genes, manipulate metabolic pathways and produce useful gene products such as hybrid antibiotics.

Isolated nucleic acids from Micromonospora rosaria plasmid pMR2 and vectors made therefrom

Three novel macrolactam monosaccharides isolated from an antimicrobial complex 510 produced in fermentation under controlled conditions using a biologically pure culture of the microorganism Actinomadura fulva subsp. uruguayensis ATCC 53713.

Actinomadura fulva subsp uruguayensis and antimicrobial complex and

A novel macrolactam monosaccharide isolated from an antimicrobial complex 517 produced in fermentation under controlled conditions using a biologically pure culture of the microorganism Actinomadura vulgaris subsp. vulgaris ATCC 53748.

Actinomadura vulgaris subsp vulgaris and antimicrobial complex and

N-alkanoyl derivatives of staurospodne represented by the formula I ##STR1## wherein R.sub.a and R.sub.b are each H or ##STR2## wherein R.sub.1 and R.sub.2 are independently H or --OH or --OCH.sub.3 and R.sub.3 is OH, NHCH.sub.3, NCH COCH.sub.3 or NHCOCH.sub.3 and R.sub.4 is OH or H and, stereochemical isomers thereof with the provisos that (1) when R.sub.a and R.sub.b .dbd.A, and R.sub.1.dbd.H.sub.2 or OH R.sub.3 is not NHCH.sub.3 ; (2) when R.sub.a and R.sub.b.dbd. B, then R.sub.1 .dbd.R.sub.4 .dbd.OH or R.sub.1 .dbd.R.sub.4 .dbd.H; (3) when R.sub.a .dbd.R.sub.b .dbd.H R.sub.1 .dbd.--OCH.sub.3, and (4) when R.sub.a and R.sub.b .dbd.A, and R.sub.1 .dbd.H and R.sub.2 .dbd.OCH.sub.3, then R3 is not and ##STR3## pharmaceutical compositions thereof useful for inhibiting myosin light chain kinase, protein kinase C or tumor cell proliferation as well as producing an antihypertensive effect and an anti-inflammatory effect in warm-blood animals such as man are disclosed.

Indolocarbazoles from saccharothrix aerocolonigenes copiosa subsp. nov

Compounds of the formulas: ##STR1## or pharmaceutically acceptable salts thereof. These compounds are obtainable by cultivation of a pure culture of Actinoplanes sp. SCC2314, ATCC 55600. These compounds are useful as antifungal agents.

Antifungal compounds

Compounds of the formula: ##STR1## wherein a is a single bond and b is a double bond; or a is a double bond and b is a single bond; and enantiomers thereof; or a pharmaceutically acceptable salt thereof are described. These compounds can improve lipoprotein profile of dyslipidemic patients and generate an anti-atherogenic lipoprotein profile of normolipidemic individuals. In addition, inhibition of CETP activity may be useful as antifertility agents.

Anti-dyslipidemic agents

Two novel glycosides of 3'-deoxyaquayamycin isolated from an antimicrobial complex produced in fermentation under controlled conditions using a biologically pure culture of the microorganism Streptomyces sp. SCC 2136, ATCC 55186 are disclosed.

Glycosides of 3'-deoxyaquayamycin antibiotics

Novel macrocyclic lactone antibacterials isolated from a culture containing the microorganism S. aerocolongenes sub sp. antibiotica SCC 1886, ATTC 55003 and their use for treating and/or preventing antibacterial infections, especially Chlamydia infections are disclosed.

Macrocyclic lactone antibacterial antibiotic compounds

A method for treating airway congestion which comprises administering an effective amount of the compound of formula II which follows ##STR1## or a pharmaceutically acceptable salt thereof.

Growing community of inventors

Summit, NJ, United States of America

Ann C Horan