Sepracor, Inc.

Biocheminsights, Inc.

Creative Biomolecules, Inc.

Azitra Inc

David R Dodds

Charles M Zepp

William B Armiger

Stephen Alan Wald

Mattheos Koffas

Stephen L Matson

Jorge Luis Lopez

Charles M Cohen

James S Huston

Ming-De Deng

Travis Michael Whitfill

Robert L Bratzler

Steven Brandt

Clifford S Morrison

Travis J Armiger

Alexander Tikhonov

Robert A Dishman

A device and process for using the device are provided for the production of commodity chemicals by biological methods which require the addition of reducing equivalents. The device allows operating conditions to be conveniently altered to achieve maximal electrochemical efficiencies for a given biologically mediated redox reaction, series of reactions, or fermentation process.

Electrochemical bioreactor module and methods of using the same

A combination of an electrochemical device for delivering reducing equivalents to a cell, and engineered metabolic pathways within the cell capable of utilizing the electrochemically provided reducing equivalents is disclosed. Such a combination allows the production of commodity chemicals by fermentation to proceed with increased carbon efficiency.

Methods and systems for 1-butanol production

A device and process for using the device are provided for the production of commodity, specialty, performance or fine chemicals by redox enzyme systems which require the addition of reducing equivalents. The device allows operating conditions to be conveniently altered to achieve maximal electrochemical efficiencies for a given enzymatically mediated redox reaction or series of reactions.

Electrochemical bioreactor module and use thereof

The present disclosure provides recombinantbacterium (e.g.) that are dependent on D-alanine for growth. In one aspect, the disclosure features a recombinantbacterium comprising two inactivated alanine racemase genes (&#x394;alr1&#x394;alr2); and an inactivated D-alanine aminotransferase (dat) gene. In another aspect, the disclosure features a method of making the recombinantbacterium.

Auxotrophic strains ofbacterium

Provided herein a re composition and process for using an electrochemical device for the reduction of the oxidized state of phosphorylated or non-phosphorylated nicotinamide adenine dinucleotide to the reduced state in which unwanted products of the electrochemical reduction are recovered as the oxidized state of the phosphorylated or non-phosphorylated nicotinamide adenine dinucleotide and returned to the electrochemical device for reduction.

Method for using electrochemical bioreactor module with recovery of cofactor

This invention relates to a method for the production of (2R,3S)-3-(4-methoxyphenyl)glycidic acids and esters thereof, which are synthetic intermediates for the production of the calcium antagonist diltiazem. The method involves the stereoselective enzymatic ester hydrolysis of racemic trans-3-(4-methoxyphenyl)glycidic acid ester to yield the resolved (2R,3S) compound as the ester. Membrane reactor methods and apparatus for the conduct of this enzymatic resolution process are also disclosed herein, as is the use of bisulfite anion in the aqueous reaction phase as a means of minimizing the inhibitory effect of an aldehyde reaction by-product on the reaction's progress. The benefits of selected solvent systems from which may be obtained highly resolved ester product are also disclosed. These enriched organic solutions may be used in subsequent transformations. Alternatively, optically pure product may be obtained directly therefrom.

Process for preparing optically active glycidate esters

This invention relates to a method for the production of (2R,3S)-3-(4-methoxyphenyl)glycidic acids and esters thereof, which are synthetic intermediates for the production of the calcium antagonist diltiazem. The method involves the stereoselective enzymatic ester hydrolysis of racemic trans-3-(4-methoxyphenyl)glycidic acid ester to yield the resolved 2R,3S compound as the ester. Membrane reactor methods and apparatus for the conduct of this enzymatic resolution process are also disclosed herein, as is the use of bisulfite anion in the aqueous reaction phase as a means of minimizing the inhibitory effect of an aldehyde reaction by-product on the reaction's progress.

Enzymatic hydrolysis of glycidate esters in the presence of bisulfite

This invention relates to novel compositions of matter which are esters with enhanced water solubility, for use in aqueous enzymatic resolution reactions of racemic mixtures of these esters for producing the separate chiral isomers of the racemic mixture. The invention also relates to novel methods for preparing these esters. The importance of the production of the separate chiral isomers of the racemic mixtures resides in the isolation of the isomers which frequently have different biological activities. Of particular significance regarding the water soluble esters of this invention is that they are derivatized with groups which enhance their aqueous solubility and their reactivity with enzymatic resolving methods which are mediated in an aqueous environment.

Compounds useful in enzymatic resolution systems and their preparation

This invention relates to novel compositions of matter which are esters with enhanced water solubility, for use in aqueous enzymatic resolution reactions of racemic mixtures of these esters for producing the separate chiral isomers of the racemic mixture. The invention also relates to novel methods for preparing these esters. The importance of the production of the separate chiral isomers of the racemic mixtures resides in the isolation of the isomers which frequently have different biological activities. Of particular significance regarding the water soluble esters of this invention is that they are derivatized with groups which enhance their aqueous solubility and their reactivity with enzymatic resolving methods which are mediated in an aqueous environment. In addition, the importance of these compounds resides in their being useful in novel methods for facilitating the enzymatic resolution reactions of racemic mixtures of esters, which are derivatized with groups which enhance the esters' aqueous solubility, in 1) a homogeneous aqueous reaction system where an extractive phase is not present, 2) a multiphase dispersion extractive reaction where an extractive phase is present, and 3) an extractive membrane reactor where the enzyme is placed alternatively either (a) in the aqueous phase, (b) in association with the membrane, or (c) in the aqueous phase and in association with the membrane, wherein the aqueous ester phase is contacted with one side of the membrane, and where an organic extractive phase is contacted with the other side of the membrane, wherein the extractive phase serves to remove the resolving reaction product.

Disclosed are processes and apparatus for separating a desired solute, such as an optically active isomer, from a complex mixture using carrier facilitated transport in an immobilized liquid membrane or carrier facilitated solvent extraction. The carrier is a binding protein selected and/or engineered to immunochemically reversibly bind to the solute and to have a significant solubility in the extracting solvent or immobilized liquid membrane.

Separation by carrier mediated transport

This invention relates to novel methods for facilitating the enzymatic resolution of racemic mixtures of esters, which are derivatized with groups which enhance the esters' aqueous solubility, in an extractive member reactor where the enzyme is placed alternatively either (1) in the aqueous phase, (2) in association with the membrane, or (3) in the aqueous phase and in association with the membrane, wherein the aqueous ester phase is contacted with one side of the membrane, and where an organic extractive phase is contacted with the other side of the membrane, wherein the extractive phase serves to remove the resolving reaction product. Of particular significance regarding this invention is its use of water soluble esters that are derivatized with groups which enhance their aqueous solubility and their reactivity with enzymatic resolving methods which are mediated in an aqueous environment. Novel methods were utilized to prepare these esters, for use in this invention's methods for enzymatically resolving the racemic mixtures of the esters, to produce the separate chiral isomers of the racemic mixture. The importance of the resolution of the separate chiral isomers of the racemic mixtures resides in the isolation of the isomers which frequently have different biological activities.

Method for membrane reactor resolution of stereoisomers

This invention relates to a novel method of effecting aqueous enzymatic and homogeneous resolutions of racemic esters which exhibit enhanced aqueous solubility. The preferred embodiment of this invention relates to the resolutions which are effected by placing the enzyme and racemic esters in an aqueous phase wherein one of the ester enantiomers is preferentially and stereospecifically de-esterified to effect the resolution of the initial racemic mixture. In another embodiment of this invention, the resolutions are effected by placing the enzyme and racemic esters in an aqueous phase, and contacting this aqueous phase with an organic phase. The preferential and stereospecific de-esterification of one of the ester enantiomers is effected, and the chiral acid product of the de-esterification reaction is extracted into the organic phase.

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Millis, MA, United States of America

David R Dodds