Abstract: Embodiment of the present invention discloses a kind of methionine lyase and its encoding gene and biosynthetic method. According to the present invention, the gene encoding methionine lyase as shown in SEQ ID No. 1 is separated from the genome of C. rosea. Embodiment of the present invention further provides an efficient biosynthetic method of methionine lyase, comprising: (1) cloning gene (shown in SEQ ID No.1) encoding methionine degradation enzyme into a yeast expression vector to construct recombinant yeast expression vector; (2) transforming the recombinant yeast expression vector into Saccharomyces cerevisiae to obtain expression strain; (3) inducing the expression strain to express the methionine lyase, collecting induced strains, purifying expressed recombinant methionine lyase. Purity of recombinant methionine lyase prepared according to the present invention is above 90%, and its efficiency of degradating methionine can reach 0.53±0.0030 ?M MTL·h?1·mg protein?1.
Type:
Grant
Filed:
December 3, 2015
Date of Patent:
June 4, 2019
Assignee:
HUBEI UNIVERSITY OF TECHNOLOGY
Inventors:
Yajie Tang, Kaizhi Jia, Yanghua Xu, Quan Zhang, Hongmei Li
Abstract: The application is directed to efficient and economical processes as described in more detail below for the preparation of the beta 3 agonists of the formula of I-7 and intermediate compounds that can be used for making these agonists. The present disclosure relates to a process for making beta-3 agonists and intermediates using ketoreductase (KRED) biocatalyst enzymes and methods of using the biocatalysts.
Type:
Grant
Filed:
March 12, 2014
Date of Patent:
May 14, 2019
Assignee:
MERCK SHARP & DOHME CORP.
Inventors:
Feng Xu, Zhuqing Liu, Richard Desmond, Jeonghan Park, Alexei Kalinin, Birgit Kosjek, Hallena Strotman, Hongmei Li, Johannah Moncecchi
Abstract: Recombinant polypeptides having UDP-glycosyltransferase activities, including a 1,2-19-O-glucose glycosylation activity and a 1,2-13-O-glucose glycosylation activity for synthesizing of steviol glucosides, are provided. A method of producing a steviol glycoside composition using such recombinant polypeptide is also provided. Also disclosed are steviol glycosides referred to as rebaudioside Z1 and rebaudioside Z2.
Abstract: The present disclosure relates to engineered ketoreductase polypeptides for the preparation of hydroxyl substituted carbamate compounds, and polynucleotides, vectors, host cells, and methods of making and using the ketoreductase polypeptides.
Type:
Grant
Filed:
September 10, 2018
Date of Patent:
April 9, 2019
Assignee:
Codexis, Inc.
Inventors:
Fabien Louis Cabirol, Haibin Chen, Anupam Gohel, Steven J. Collier, Derek J. Smith, Birgit Kosjek, Jacob Janey
Abstract: The present disclosure provides engineered ketoreductase enzymes having improved properties as compared to a naturally occurring wild-type ketoreductase enzyme including the capability of reducing 5-((4S)-2-oxo-4-phenyl (1,3-oxazolidin-3-yl))-1-(4-fluorophenyl) pentane-1,5-dione to (4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidin-2-one. Also provided are polynucleotides encoding the engineered ketoreductase enzymes, host cells capable of expressing the engineered ketoreductase enzymes, and methods of using the engineered ketoreductase enzymes to synthesize the intermediate (4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidin-2-one in a process for making Ezetimibe.
Abstract: Methods and systems for the production of alcohols are described. A two stage process is utilized, where fermentation in a first stage produces an intermediate product, such as an amino acid or organic acid, from a carbon containing feedstock. A second stage produces alcohol by fermentation of this intermediate product.
Abstract: The present invention provides for a genetically modified host cell comprising a 2-pyrrolidone synthase, or an enzymatically active fragment thereof, heterologous to the host cell.
Type:
Grant
Filed:
April 14, 2016
Date of Patent:
March 12, 2019
Assignee:
The Regents of the University of California
Abstract: Described herein is a chemostat-like continuous cell culture system that combines certain advantages of perfusion open systems and chemostat open systems to improve the culturing of mammalian cells, e.g., genetically modified cells, particularly in serum-free or chemically-defined media. The continuous culture system described herein involves culturing mammalian cells in a continuous cell culture system, which comprises a cell retention device, wherein the cell culture system has a dilution rate (D) of less than about 2 d?1, and a cell density of less than about 2×107 cell/mL.
Type:
Grant
Filed:
April 12, 2017
Date of Patent:
March 5, 2019
Assignees:
Baxalta GmbH, Baxalta Incorporated
Inventors:
Leopold Grillberger, Manfred Reiter, Daniel Fleischanderl
Abstract: Carbon-containing materials, such as biomass (e.g., plant biomass, animal biomass, and municipal waste biomass) or coal are processed to produce useful products, such as fuels, carboxylic acids and equivalents thereof (e.g., esters and salts). For example, systems are described that can use feedstock materials, such as cellulosic and/or lignocellulosic materials and/or starchy materials, to produce ethanol, butanol or organic acids (e.g., acetic or lactic acid), salts of organic acids or mixtures thereof. If desired, organic acids can be converted into alcohols, such as by first converting the acid, salt or mixtures of the acid and its salt to an ester, and then hydrogenating the formed ester. Acetogens or homoacetogens which are capable of utilizing a syngas from a thermochemical conversion of coal or biomass can be utilized to produce the desired product.
Type:
Grant
Filed:
January 31, 2018
Date of Patent:
February 12, 2019
Assignee:
XYLECO, INC.
Inventors:
Marshall Medoff, Thomas Craig Masterman
Abstract: In certain aspects, the present invention provides methods for producing terminally hydroxylated alkenes and alkynes by contacting an unsaturated or saturated hydrocarbon substrate with a hydroxylase enzyme. Exemplary terminal hydroxylases useful for carrying out the methods of the invention exhibit strong selectivity towards one terminal carbon of a hydrocarbon substrate and include, but are not limited to, non-heme diiron alkane monooxygenases, cytochromes P450 (e.g., cytochromes P450 of the CYP52 and CYP153 family), as well as long chain alkane hydroxylases. In some embodiments, the terminally hydroxylated alkene or alkyne is further converted to a terminal alkenal. In certain embodiments, terminally hydroxylated alkenes and alkynes are useful as insect pheromones which modify insect behavior. In other embodiments, terminally hydroxylated alkenes and alkynes are useful intermediates for producing pheromones via acetylation or oxidation of the alcohol moiety.
Type:
Grant
Filed:
September 3, 2015
Date of Patent:
February 12, 2019
Assignee:
PROVIVI, INC.
Inventors:
Pedro Coelho, Mike M. Y. Chen, Peter Meinhold, Catherine Mee-Hie Cho, Vu Bui, Thomas Heel
Abstract: The present disclosure relates to the use of an amino acid dehydrogenase in combination with a cofactor regenerating system comprising a ketoreductase. In particular embodiments, the process can be used to prepare L-tert-leucine using a leucine dehydrogenase.
Type:
Grant
Filed:
June 20, 2017
Date of Patent:
February 5, 2019
Assignee:
Codexis, Inc.
Inventors:
Fabien Louis Cabirol, Steven J. Collier, Thomas Daussmann, Naga K. Modukuru
Abstract: Disclosed herein are botulinum neurotoxin (BoNT) polypeptides with a modified receptor binding domain of Clostridial botulinum serotype B (B-Hc), comprising one or more substitution mutations corresponding to substitution mutations in serotype B, strain 1, V1118M; Y1183M; E1191M; E1191I; E1191Q; E1191T; S1199Y; S1199F; S1199L; S1201V; or combinations thereof. Specific combination mutations include E1191M and S1199L, E1191M and S1199Y, E1191M and S1199F, E1191Q and S1199L, E1191Q and S1199Y, or E1191Q and S1199F. Other substitution mutations are also disclosed. Isolated modified receptor binding domains, chimeric molecules, pharmaceutical compositions, and methods of using the same are also disclosed.
Type:
Grant
Filed:
February 13, 2017
Date of Patent:
January 29, 2019
Assignee:
PRESIDENT AND FELLOWS OF HARVARD COLLEGE
Inventors:
Min Dong, Lisheng Peng, Pål Erik Gustav Stenmark, Ronnie Per Arne Berntsson
Abstract: The present invention relates to novel mutants with cyclase activity and use thereof in a method for biocatalytic cyclization of terpenes, such as in particular for the production of isopulegol by cyclization of citronellal; a method for the preparation of menthol and methods for the biocatalytic conversion of further compounds with structural motifs similar to terpene.
Type:
Grant
Filed:
August 11, 2016
Date of Patent:
January 29, 2019
Assignee:
BASF SE
Inventors:
Michael Breuer, Bernhard Hauer, Dieter Jendrossek, Gabriele Siedenburg, Juergen Pleiss, Demet Sirim, Silvia Fadenrecht
Abstract: The present invention relates to a method for extracorporeal removal of a pathogenic microbe, an inflammatory cell or an inflammatory protein from mammalian blood/use of a device comprising a carbohydrate immobilized on a solid substrate, said carbohydrate having a binding affinity for a pathogenic microbe, an inflammatory cell or an inflammatory protein, for extracorporeal removal of said pathogenic microbe, inflammatory cell or inflammatory protein from mammalian blood/use of a carbohydrate having a binding affinity for a pathogenic microbe, an inflammatory cell or an inflammatory protein, wherein said carbohydrate is immobilized on a solid substrate, in the preparation of a device for treatment of a condition caused or aggravated by said pathogenic microbe, inflammatory cell or inflammatory protein and a method for treatment of a mammalian subject suffering from a condition caused or aggravated by a pathogenic microbe, an inflammatory cell or an inflammatory protein.
Abstract: A biocatalytic process for producing active pharmaceutical ingredients (APIs) or intermediates thereof, wherein those APIs or their intermediates are nucleoside analogues (NAs) of formula I and wherein said NAs are active as pharmaceutically relevant antivirals and anticancer medicaments, intermediates or prodrugs thereof.
Type:
Grant
Filed:
April 29, 2014
Date of Patent:
January 22, 2019
Assignee:
Plasmia Biotech, S.L.
Inventors:
Marta Pascual Gilabert, Victor Manuel Deroncelé Thomas, Rafael Montilla Arévalo
Abstract: The present invention relates to a novel process for cyclizing geranyllinalool using the squalene-hopene cyclase from Zymomonas mobilis (Zm-SHC) or a cyclase with at least 80% sequence identity to the Zm-SHC, and cyclization products obtained in this process.
Abstract: The present invention relates to a method of preparing at least one rhamnolipid comprising: contacting a recombinant cell with a medium containing a carbon source; and culturing the cell under suitable conditions for preparation of the rhamnolipid from the carbon source by the cell, wherein the recombinant cell has been genetically modified such that, compared to the wild-type of the cell, the cell has an increased activity of at least one of the enzymes E1, E2 and E3, wherein the enzyme E1 is an ?/? hydrolase, the enzyme E2 is a rhamnosyltransferase I and the enzyme E3 is a rhamnosyl-transferase II, and wherein the carbon source is a C4 molecule.
Type:
Grant
Filed:
April 27, 2015
Date of Patent:
January 8, 2019
Assignee:
Evonik Degussa GmbH
Inventors:
Oliver Thum, Philip Engel, Christian Gehring, Steffen Schaffer, Mirja Wessel
Abstract: The invention provides a fusion protein comprising, from N-terminus to C-terminus: a) a first portion of a Family B G-protein coupled receptor (GPCR) that comprises transmembrane helix (TM)-1, TM2 and TM3 of the GPCR; b) a stable protein domain; and c) a second portion of the GPCR comprising TM4, TM5, TM6 and TM7 of the GPCR. The invention also provides a method of crystallizing a GPCR comprising providing the fusion protein of the invention and crystallizing it to obtain crystals.
Type:
Grant
Filed:
August 9, 2012
Date of Patent:
January 8, 2019
Assignee:
Heptares Therapeutics Limited
Inventors:
Seyed Ali Jazayeri-Dezfuly, Fiona Hamilton Marshall
Abstract: The invention relates to enzymatic methods for hydroxylation in position 2 or 3 of substituted or unsubstituted, linear or branched aliphatic hydrocarbons.
Type:
Grant
Filed:
February 2, 2018
Date of Patent:
January 8, 2019
Assignee:
Novozymes A/S
Inventors:
Martin Hofrichter, Katrin Scheibner, Rene Ullrich, Matthias Kinne, Sebastian Peter, Henrik Lund, Lisbeth Kalum