专利号:US-11447742-B2 优先权日:2016-02-09 标题 :Compositions and methods for activation and overexpression of secondary metabolites in microorganisms 发明人:HAMILL DAKOTA BENJAMIN; COTTER JAKE J 权利人:PROSPECTIVE RES INC 摘要:Methods and compositions herein provide non-naturally occurring γ-butyrolactones (GBLs) in racemic mixtures that increase efficiency and effectiveness of screening for production of antibiotics, and enhance yields and express silent pathways. Non-naturally occurring GBLs were synthesized and found to stimulate antibiotic production in several different streptomycete strains. Antibiotic production by Streptomyces coelicolor was induced by a racemic mixture of non-cognate stereoisomers of VB-D, seven of which are non-naturally occurring. Further, novel A-factor-type GBL analogs stimulated antibiotic production in S. coelicolor . Synthesis in response to the treatment with the non-cognates GBL was observed for known compounds including undecylprodigiosin, desferrioxamine and streptorubin B, as was synthesis of a compound of unknown structure. A group of 37 additional microbial strains was screened by principal component analysis to determine optimal concentrations of each of a panel of four non-cognate synthetic GBLs for addition to cultures with optimal stimulation of secondary metabolites, and large scale fermentations were analyzed and product enhancement by the GBLs was observed.
专利号:US-5662898-A 优先权日:1990-08-20 标 题 :Genes for the synthesis of antipathogenic substances 发明人:LIGON JAMES M; HILL DWIGHT STEVEN; LAM STEPHEN TING; HAMMER PHILIP E 权利人:CIBA GEIGY CORP 摘要:The present invention is directed to the production of an antipathogenic substance (APS) in a host via recombinant expression of the polypeptides needed to biologically synthesize the APS. Genes encoding polypeptides necessary to produce particular antipathogenic substances are provided, along with methods for identifying and isolating genes needed to recombinantly biosynthesize any desired APS. The cloned genes may be transformed and expressed in a desired host organisms to produce the APS according to the invention for a variety of purposes, including protecting the host from a pathogen, developing the host as a biocontrol agent, and producing large, uniform amounts of the APS.
专利号:US-9115358-B2 优先权日:2006-08-11 标题 :Moenomycin biosynthesis-related compositions and methods of use thereof 发明人:WALKER SUZANNE; OMELYANOVICH OSTASH BOHDAN 权利人:WALKER SUZANNE; OMELYANOVICH OSTASH BOHDAN; HARVARD COLLEGE 摘要:The methods and compositions described herein relate to the identification, isolation, and characterization of genes which encode proteins useful for the biosynthesis of transglycosylase inhibitors such as moes. The methods and compositions also relate to the production of such proteins, and their use in the synthesis of moes, the expression of moes, and the production of modified moes.
专利号:US-2023399688-A1 优先权日:2015-08-20 标 题 :Compositions and multiplexed systems for coupled cell-free transcription-translation and protein synthesis and methods for using them 发明人:CULLER STEPHANIE; CHEN IHSIUNG BRANDON; PHARKYA PRITI; VAN DIEN STEVE; BARTON NELSON 权利人:GENOMATICA INC 摘要:In alternative embodiments, provided herein are transcription/translation (TX-TL) systems and methods of using them for use as rapid prototyping platforms for the synthesis, modification and identification of natural products (NPs), and natural product analogs (NPAs) and secondary metabolites, from biosynthetic gene cluster pipelines. In alternative embodiments, exemplary TX-TL systems as provided herein are used for the combinatorial biosynthesis of natural products (NPs), natural product analogs (NPAs) and secondary metabolites. In alternative embodiments, exemplary TX-TL systems as provided herein are used for the rapid prototyping of complex biosynthetic pathways as a way to rapidly assess combinatorial and biosynthetic designs before moving to cellular hosts. In alternative embodiments, these exemplary TX-TL systems are multiplexed for high-throughput (HT) automation and for prototyping engineered platforms for the synthesis or modification of natural products (NPs), and natural product analogs (NPAs) and secondary metabolites analogs.
专利号:US-6290966-B1 优先权日:1999-07-09 标 题:Dim mutants of mycobacteria and use thereof 发明人:COX JEFFERY S; JACOBS JR WILLIAM R 权利人:EINSTEIN COLL MED 摘要:Disclosed are novel recombinant mutant strains of mycobacteria that are deficient for the synthesis or transport of dimycoserosalphthiocerol (“DIMâ€?). The present invention also provides a method of producing a recombinant mutant mycobacterium that is deficient for the synthesis or transport of DIM, comprising mutating a nucleic acid responsible for the synthesis or transport of dimycoserosalphthiocerol, including a nucleic acid comprising the promoter for the pps operon, fadD28 or mmpL7. The present invention also provides a vaccine comprising a DIM mutant mycobacterium of the present invention, as well as a method for the treatment or prevention of tuberculosis in a subject using the vaccine.
专利号:EP-0468217-B1 优先权日:1990-07-26 标 题 :A bifunctional cosmid useful for cloning actinomycete DNA 发明人:RYAN MICHAEL J; LOTVIN JASON A; STRATHY NANCY 权利人:AMERICAN CYANAMID CO 摘要:The present invention relates to novel and useful cosmids for cloning and expressing the isolated DNA gene cluster which directs the synthesis of tetracycline and chlortetracycline, in a heterologous host such as Streptomyces lividans. The claimed plasmids (cosmids) are isolated by screening a cosmid library, constructed in Escherichia coli, for the expression of tetracycline resistance in S. lividans. Plasmids LP<2>127 and LP<2>128 are recovered from such tetracycline-resistant S. lividans isolates shown by HPLC analysis of agar and broth fermentations to direct the synthesis of tetracycline and chlortetracycline.
参考文献:10.1186/1477-5956-9-40 摘要:Luo Y, Ding X, Xia L, Huang F, Li W, Huang S, Tang Y, Sun Y. Comparative Proteomic Analysis of saccharopolyspora spinosa SP06081 and PR2 strains reveals the differentially expressed proteins correlated with the increase of spinosad yield. Proteome Sci. 2011 Jul 16;9():40. 参考文献:10.1371/journal.pone.0021974 摘要:Chatterjee A, Drews L, Mehra S, Takano E, Kaznessis YN, Hu W. Convergent Transcription in the Butyrolactone Regulon in Streptomyces coelicolor Confers a Bistable Genetic Switch for Antibiotic Biosynthesis. PLoS ONE. 2011 Jul 12;6(7):e21974. doi: 10.1371/journal.pone.0021974. 参考文献:10.1186/1471-2180-11-164 摘要:Pan Y, Wang L, He X, Tian Y, Liu G, Tan H. SabR enhances nikkomycin production via regulating the transcriptional level of sanG, a pathway-specific regulatory gene in Streptomyces ansochromogenes. BMC Microbiology. 2011 Jul 20;11(1):164. doi: 10.1186/1471-2180-11-164. 参考文献:10.1021/bi2006866 摘要:Javidpour P, Das A, Khosla C, Tsai SC. Structural and biochemical studies of the hedamycin type II polyketide ketoreductase (HedKR): molecular basis of stereo- and regiospecificities. Biochemistry. 2011 Aug 30;50(34):7426–39.