- Design and Use of de novo Cascades for the Biosynthesis of New Benzylisoquinoline Alkaloids
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The benzylisoquinoline alkaloids (BIAs) are an important group of secondary metabolites from higher plants and have been reported to show significant biological activities. The production of BIAs through synthetic biology approaches provides a higher-yielding strategy than traditional synthetic methods or isolation from plant material. However, the reconstruction of BIA pathways in microorganisms by combining heterologous enzymes can also give access to BIAs through cascade reactions. Most importantly, non-natural BIAs can be generated through such artificial pathways. In the current study, we describe the use of tyrosinases and decarboxylases and combine these with a transaminase enzyme and norcoclaurine synthase for the efficient synthesis of several BIAs, including six non-natural alkaloids, in cascades from l-tyrosine and analogues.
- Wang, Yu,Tappertzhofen, Nadine,Méndez-Sánchez, Daniel,Bawn, Maria,Lyu, Boyu,Ward, John M.,Hailes, Helen C.
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p. 10120 - 10125
(2019/06/27)
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- Compositions and methods for producing benzylisoquinoline alkaloids
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The present invention relates to host cells that produce compounds that are characterized as benzylisoquinolines, as well as select precursors and intermediates thereof. The host cells comprise one, two or more heterologous coding sequences wherein each of the heterologous coding sequences encodes an enzyme involved in the metabolic pathway of a benzylisoquinoline, or its precursors or intermediates from a starting compound. The invention also relates to methods of producing the benzylisoquinoline, as well as select precursors and intermediates thereof by culturing the host cells under culture conditions that promote expression of the enzymes that produce the benzylisoquinoline or precursors or intermediates thereof.
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- One-pot triangular chemoenzymatic cascades for the syntheses of chiral alkaloids from dopamine
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We describe novel chemoenzymatic routes to (S)-benzylisoquinoline and (S)-tetrahydroprotoberberine alkaloids using the enzymes transaminase (TAm) and norcoclaurine synthase (NCS) in a one-pot, one-substrate 'triangular' cascade. Employment of up to two C-
- Lichman,Lamming,Pesnot,Smith,Hailes,Ward
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supporting information
p. 852 - 855
(2015/03/04)
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- The catalytic potential of Coptis japonica NCS2 revealed - Development and utilisation of a fluorescamine-based assay ETI
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The versatility and potential of a norcoclaurine synthase (NCS) from Coptis japonica NCS2 has been investigated, together with the development and application of a novel fluorescence-based high-throughput assay using nearly forty amines/aldehydes. The stereocontrol exerted by CjNCS2 on selected non-natural substrates has been determined, where the tetrahydroisoquinolines (THIAs) were formed as the (1S)-isomer in >95% ee, as observed with the natural product norcoclaurine. Docking calculations involving THIA mechanism intermediates, utilising the reported Thalictrum flavum NCS X-ray crystallographic structure, were carried out and combined with the CjNCS2 screening results to further understand the mode of action of NCS. These findings suggested that in addition to the key active-site residues K122 and E110, D141 is also mechanistically essential for the enzymatic transformation. The exceptional tolerance of NCS towards aldehyde substrates is furthermore supported by our proposed mechanism in which the aldehydes protrude out of the enzymatic pocket. Copyright
- Pesnot, Thomas,Gershater, Markus C.,Ward, John M.,Hailes, Helen C.
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p. 2997 - 3008
(2013/01/15)
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- Acid-Degradable and Bioerodible Modified Polyhydroxylated Materials
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Compositions and methods of making a modified polyhydroxylated polymer comprising a polyhydroxylated polymer having reversibly modified hydroxyl groups, whereby the hydroxyl groups are modified by an acid-catalyzed reaction between a polydroxylated polyme
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- Imaging agents for detecting neurological disorders
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Imaging agents of formula (I) and methods for detecting neurological disorders comprising administering to a patient in need compounds of formula (I) capable of binding to tau proteins and β-amyloid peptides are presented herein. The invention also relates to methods of imaging Aβ and tau aggregates comprising introducing a detectable quantity of pharmaceutical formulation comprising a radiolabeled compound of formula (I) and detecting the labeled compound associated with amyloid deposits and/or tau proteins in a patient. These methods and compositions enable preclinical diagnosis and monitoring progression of AD and other neurological disorders.
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- 2-(PYRAZOL-1-YL)PYRIDINE DERIVATIVE
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Inventors found that a compound shown by formula: can be produced efficiently by using a compound shown by formula: (wherein R is a protected hydroxy or a group shown by: (wherein R1 is alkyl or optionally substituted aralkyl, and R2 is alkyl)).
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- Remedies
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The present invention provides a therapeutic agent or prophylactic agent for a disease that requires enhancement of nerve growth factor production, an enhancer for nerve growth factor production, or a food, beverage or feed for enhancing nerve growth fact
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- Triple polypeptide complexes
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The invention provides methods and materials related to treating and diagnosing autoimmune conditions. Specifically, the invention provides polypeptide compositions, nucleic acids, substantially pure polypeptides, host cells, and methods for identifying a mammal with an autoimmune condition, treating a mammal with an autoimmune condition, and enhancing tolerance in a mammal with an autoimmune condition.
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- 4-haloalkyl-3-heterocyclylpyridines and 4-haloalkyl-5-heterocyclylpyrimidines, processes for their preparation, compositions comprising them, and their use as pesticides
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The present invention relates to 4-haloalkyl-3-heterocyclylpyridines and 4-haloalkyl-5-heterocyclylpyrimidines of the formula (I), to processes for their preparation, to compositions comprising them, and to the use of these compounds for controlling anima
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- Hydroxymethyl phosphine compounds for use as diagnostic and therapeutic pharmaceuticals and method of making same
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A compound and method of making a compound for use as a diagnostic or therapeutic pharmaceutical comprises at least one functionalized hydroxyalkyl phosphine donor group and one or more sulfur or nitrogen donor and a metal combined with the ligand.
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- Process for the preparation of cephem prodrug esters
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The invention relates to a process for the preparation of cephem prodrug esters of the formula: STR1 in which R1 is C1 -C5 -alkanoyloxy-C1 -C3 -alkyl or C1 -C5 -alkoxycarbonyloxy
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- Acylated hindered hexahydropyrimidines and their use as light stabilizing agents
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An acylated, hindered hexahydropyrimidine of the formula STR1 wherein R1, R2, R3 and R4 may be the same or different independently of each other and are alkyl having 1 to 6 carbon atoms, when unsubstituted, or alkyl or aryl substituted; R5 and R6 may be the same or different and are hydrogen, or alkyl; R7 is selected from the group consisting of: alkyl having 1 to 20 carbon atoms, substituted alkyl where the alkyl without substitution has 1 to 20 carbon atoms and where substituents may be up to five lower alkyl groups, arylalkyl, cycloalkyl having 3 to 12 carbon atoms, aryl aryl substituted with 1 to 3 substituents seleted from the group consisting of: lower alkyl, lower alkoxy, and hydroxyl; STR2 wherein R9 is unsubstituted or substituted with alkyl, R10 is hydroxyl, lower alkoxy, phenoxy and the group STR3 and R8 is hydrogen, alkyl, substituted alkyl, arylalkyl, hydroxyl, oxyl and STR4 wherein R11 is unsubstituted or substituted alkyl.
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- Process for preparing vitamin D-lactones
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The invention provides methods for preparing the various isomeric forms of 25-hydroxyvitamin D3 -26,23-lactone utilizing cyanohydrin formation with readily prepared steroid materials followed by actinic radiation of the products and recovery of the desired 25-hydroxyvitamin D3 -26,23-lactone. The invention also provides new intermediate compounds in their various isomeric forms derived during the process for preparing the said vitamin D3 lactones. 25-Hydroxyvitamin D3 -26,23-lactone is recognized as having vitamin D-like activity and is believed to play an important role in the regulation of calcium and phosphate levels in the animal and human organism. The present invention provides a convenient method for preparing the various isomeric forms of this compound.
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- 8β,12α,15β-PGE2 compounds
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This invention is a group of 8-beta, 12-alpha-PG2 (prostaglandin-type) analogs having variable chain length, or methyl or phenyl substitution in the hydroxy-substituted side-chain, and processes for making them. These compounds are useful for a variety of pharmacological purposes, including anti-ulcer, inhibition of platelet aggregation, increase of nasal patency, and labor inducement at term.
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- 8β,12α-PGE2 -type compounds
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This invention is a group of 8-beta, 12-alpha-PG2 (prostaglandin-type) analogs having variable chain length, or methyl or phenyl substitution in the hydroxy-substituted side-chain, and processes for making them. These compounds are useful for a variety of pharmacological purposes, including anti-ulcer, inhibition of platelet aggregation, increase of nasal patency, and labor inducement at term.
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- 3-Oxa prostaglandin Fα-type compounds
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This invention is a group of 3- and 4-oxa PG type compounds, and processes for making them. These compounds are useful for a variety of pharmacological purposes, including anti-ulcer, inhibition of platelet aggregation, increase of nasal patency, labor inducement at term, and wound healing.
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