Abstract: Provided herein is a non-naturally occurring microbial organism having a methanol metabolic pathway (MMP) that can enhance the availability of reducing equivalents in the presence of methanol. Such reducing equivalents can be used to increase the product yield of organic compounds produced by the microbial organism, such as 1,4-butanediol (BDO). Also provided herein are methods for using such an organism to produce BDO.
Type:
Grant
Filed:
July 3, 2023
Date of Patent:
June 30, 2026
Assignee:
Genomatica, Inc.
Inventors:
Anthony P. Burgard, Robin E. Osterhout, Stephen J. Van Dien, Cara Ann Tracewell, Priti Pharkya, Stefan Andrae
Abstract: The disclosure relates to recombinant host cells including strain modifications effective to improve titer, yield and/or productivity of fatty acid derivatives. The disclosure further relates to cell cultures including the recombinant host cells for the fermentative production of fatty acid derivatives and compositions thereof.
Type:
Grant
Filed:
June 29, 2023
Date of Patent:
June 23, 2026
Assignee:
Genomatica, Inc.
Inventors:
Derek L. Greenfield, Andreas W. Schirmer, Elizabeth J. Clarke, Eli S. Groban, Bernardo M. Da Costa, Zhihao Hu, Kevin Holden, Noah Helman
Abstract: Recombinant proteobacteria, including ?-proteobacteria, comprising a heterologous acyl-ACP desaturase and a heterologous acyl-ACP thioesterase, wherein the native dual 3-hydroxy acyl-ACP dehydratase/isomerase is deleted are provided herein. The recombinant proteobacteria produce non-native monounsaturated free fatty acids or derivatives thereof. Methods of producing non-native monounsaturated free fatty acids or derivatives thereof are also provided, in addition to cell cultures and fatty acid compositions produced by the recombinant proteobacteria. The recombinant proteobacteria may be used to produce insect pheromones or precursors thereof, and fragrances or precursors thereof.
Type:
Grant
Filed:
March 22, 2022
Date of Patent:
June 9, 2026
Assignee:
GENOMATICA, INC.
Inventors:
Andreas W. Schirmer, Erin Frances Perry, Alma Itzel Ramos-Solis, Angelica Zabala-Bautista
Abstract: The disclosure relates to omega-hydroxylated fatty acid derivatives and methods of producing them. Herein, the disclosure encompasses a novel and environmentally friendly production method that provides omega-hydroxylated fatty acid derivatives at high purity and yield. Further encompassed are recombinant microorganisms that produce omega-hydroxylated fatty acid derivatives through selective fermentation.
Type:
Grant
Filed:
March 5, 2024
Date of Patent:
April 7, 2026
Assignee:
Genomatica, Inc.
Inventors:
Andreas W. Schirmer, Haibo Wang, Stephen B. Del Cardayre, Zhihao Hu, Louis G. Hom, Baolong Zhu, Cindy Chang, Emanuela E. Popova
Abstract: The disclosure relates to methods for the production of natural lactones by bacteria under physiological conditions. The methods employ ybgC proteins having lactonizing activity.
Type:
Grant
Filed:
January 15, 2020
Date of Patent:
April 7, 2026
Assignee:
Genomatica, Inc.
Inventors:
Andreas W. Schirmer, Katherine Ann Murphy, Angelica Zabala Bautista
Abstract: Disclosed are biosynthetic methods and engineered microorganism that enhance or improve the biosynthesis of hexamethylenediamine, caproic acid or caprolactam. The engineered microorganisms include selected aldehyde dehydrogenase activity.
Abstract: The present disclosure provides microbial organisms having increased availability of co-factors, such as NADPH, for increasing production of various products, including 1,3-BDO, MMA, (3R)-hydroxybutyl (3R)-hydroxybutyrate, amino acids, 3HB-CoA, adipate, caprolactam, 6-ACA, HMD A, or MAA, and products made from any of these. Also provided are one or more exogenous nucleic acids encoding an enzyme expressed in a sufficient amount to increase availability of NADPH, where the exogenous nucleic acid includes one or more of ATP-NADH kinase, pntAB, nadK, and gapN. Also provided are one or more gene attenuations occurring in genes, such as NDH-2, that result in an increased ratio of NADPH to NADH. Various combinations of the exogenous nucleic acids and gene deletions are also provided in the present disclosure. The present disclosure also provides methods of making and using the same, including methods for culturing cells, and for the production of the various products.
Type:
Grant
Filed:
October 22, 2020
Date of Patent:
March 17, 2026
Assignee:
Genomatica, Inc.
Inventors:
Harish Nagarajan, Gionata Scalcinati, Tae Hoon Yang
Abstract: Described herein are fusion proteins including methanol dehydrogenase (MeDH) and at least one other polypeptide such as 3-hexulose-6-phosphate dehydrogenase (HPS) or 6-phospho-3-hexuloisomerase (PHI), such as DHAS synthase or fructose-6-Phosphate aldolase or such as DHA synthase or DHA kinase. In a localized manner, the fusion protein can promote the conversion of methanol to formaldehyde and then to a ketose phosphate such as hexulose 6-phosphate or then to DHA and G3P. When expressed in cells, the fusion proteins can promote methanol uptake and rapid conversion to the ketose phosphate or to the DHA and D3P, which in turn can be used in a pathway for the production of a desired bioproduct. Beneficially, the rapid conversion to the ketose phosphate or to the DHA and G3P can avoid the undesirable accumulation of formaldehyde in the cell.
Type:
Grant
Filed:
September 13, 2022
Date of Patent:
January 27, 2026
Assignee:
Genomatica, Inc.
Inventors:
Nelson R. Barton, Jingyi Li, Joseph R. Warner, Priti Pharkya
Abstract: The invention provides non-naturally occurring microbial organisms containing enzymatic pathways and/or metabolic modifications for enhancing carbon flux through acetyl-CoA. In some embodiments, the microbial organisms of the invention having such pathways also include pathways for generating reducing equivalents, formaldehyde fixation and/or formate assimilation. The enhanced carbon flux through acetyl-CoA, in combination with pathways for generating reducing equivalents, formaldehyde fixation and/or formate assimilation can, in some embodiments, be used for production of a bioderived compound. Accordingly, in some embodiments, the microbial organisms of the invention can include a pathway capable of producing a bioderived compound of the invention.
Type:
Grant
Filed:
December 20, 2023
Date of Patent:
January 20, 2026
Assignee:
Genomatica, Inc.
Inventors:
Robin E. Osterhout, Anthony P. Burgard, Priti Pharkya, Stefan Andrae
Abstract: The disclosure relates to downstream processing of fatty alcohol (FALC) and provides a novel purification method that provides FALC at high purity and yield.
Type:
Grant
Filed:
June 14, 2023
Date of Patent:
January 6, 2026
Assignee:
Genomatica, Inc.
Inventors:
Myong Ko, Haibo Wang, Patricia J. Cole, Perry Y. Liao, Simon Li
Abstract: Provided is a method of producing and isolating a diamine produced by microbial fermentation that minimizes undesirable salt formation to provide a lower cost process.
Type:
Grant
Filed:
May 22, 2023
Date of Patent:
December 23, 2025
Assignee:
Genomatica, Inc.
Inventors:
Lauri H. Suominen, Connor J. Galleher, Michael Japs, Mark J. Burk, Cara Tracewell
Abstract: The invention is directed to a non-naturally occurring microbial organism comprising a first attenuation of a succinyl-CoA synthetase or transferase and at least a second attenuation of a succinyl-CoA converting enzyme or a gene encoding a succinate producing enzyme within a multi-step pathway having a net conversion of succinyl-CoA to succinate.
Type:
Grant
Filed:
August 22, 2023
Date of Patent:
October 7, 2025
Assignee:
Genomatica, Inc.
Inventors:
Anthony P. Burgard, Robin E. Osterhout, Stephen J. Van Dien, Priti Pharkya, Tae Hoon Yang, Jungik Choi
Abstract: Disclosed are biosynthetic methods and engineered microorganisms that enhance or improve the biosynthesis of 6-aminocaproate, hexamethylenediamine, caproic acid, caprolactone, or caprolactam. The engineered microorganisms are modified to include, for example, upredulated and/or exogenous transporters for 6-aminocaproate, deletions and/or downregulated importers for 6-aminocaproate, upregulated and/or exogenous glutamate dehydrogenase, and/or deletions and/or downregulation of rcsA and/or cpsBG. Other engineered microorganisms may have disruptions of endogenous transporters for 6-aminocaproate.
Type:
Application
Filed:
January 15, 2022
Publication date:
October 2, 2025
Applicant:
Genomatica, Inc.
Inventors:
Harish Nagarajan, Tae Hoon Yang, Ali Khodayari, Shawn Bachan, Sankha Ghatak, Nicholas Eakley, Amit Shah, Jinel Shah, Bo Zhang
Abstract: The disclosure relates to enzyme variants with improved ester synthase properties for the production of fatty acid esters. Further contemplated are recombinant host cells that express such variants, cell cultures comprising the recombinant host cells and fatty acid ester compositions produced by such recombinant host cells.
Type:
Grant
Filed:
May 13, 2024
Date of Patent:
August 26, 2025
Assignee:
Genomatica, Inc.
Inventors:
Andrew M. Shumaker, Bernardo M. T. Da Costa, Kevin Holden, Louis G. Hom, Tarah S. Baron, Noah Helman
Abstract: The invention provides non-naturally occurring microbial organisms having a formaldehyde fixation pathway, a formate assimilation pathway, and/or a methanol metabolic pathway in combination with a fatty alcohol, fatty aldehyde, fatty acid or isopropanol pathway, wherein the microbial organisms selectively produce a fatty alcohol, fatty aldehyde or fatty acid of a specified length or isopropanol. The microbial organisms provided advantageously enhance the production of substrates and/or pathway intermediates for the production of chain length specific fatty alcohols, fatty aldehydes, fatty acids or isopropanol. In some aspects, the microbial organisms of the invention have select gene disruptions or enzyme attenuations that increase production of fatty alcohols, fatty aldehydes or fatty acids. The invention additionally provides methods of using the above microbial organisms to produce a fatty alcohol, a fatty aldehyde, a fatty acid or isopropanol.
Type:
Grant
Filed:
November 1, 2021
Date of Patent:
August 26, 2025
Assignee:
Genomatica, Inc.
Inventors:
Robin E. Osterhout, Anthony P. Burgard, Priti Pharkya, Stefan Andrae
Abstract: The invention provides polypeptides and encoding nucleic acids of aldehyde dehydrogenase variants. The invention also provides cells expressing aldehyde dehydrogenase variants. The invention further provides methods for producing 3-hydroxybutyraldehyde (3-HBal) and/or 1,3-butanediol (1,3-BDO), or an ester or amide thereof, comprising culturing cells expressing an aldehyde dehydrogenase variant or using lysates of such cells. The invention additional provides methods for producing 4-hydroxybutyraldehyde (4-HBal) and/or 1,4-butanediol (1,4-BDO), or an ester or amide thereof, comprising culturing cells expressing an aldehyde dehydrogenase variant or using lysates of such cells.
Abstract: The invention provides non-naturally occurring microbial organisms having a 4-hydroxybutyrate, gamma-butyrolactone, 1,4-butanediol, 4-hydroxybutanal, 4-hydroxybutyryl-CoA and/or putrescine pathway and being capable of producing 4-hydroxybutyrate, wherein the microbial organism comprises one or more genetic modifications. The invention additionally provides methods of producing 4-hydroxybutyrate, gamma-butyrolactone, 1,4-butanediol, 4-hydroxybutanal, 4-hydroxybutyryl-CoA and/or putrescine or related products using the microbial organisms.
Type:
Grant
Filed:
June 23, 2016
Date of Patent:
May 27, 2025
Assignee:
Genomatica, Inc.
Inventors:
Priti Pharkya, Anthony P. Burgard, Stephen J. Van Dien, Robin E. Osterhout, Mark J. Burk, John D. Trawick, Michael P. Kuchinskas, Brian Steer, Stefan Andrae, Amit Shah
Abstract: Provided herein is a non-naturally occurring microbial organism having a methanol metabolic pathway that can enhance the availability of reducing equivalents in the presence of methanol. Such reducing equivalents can be used to increase the product yield of organic compounds produced by the microbial organism, such as 1,4-butanediol (BDO). Also provided herein are methods for using such an organism to produce BDO.
Type:
Grant
Filed:
April 14, 2017
Date of Patent:
April 1, 2025
Assignee:
Genomatica, Inc.
Inventors:
Anthony P. Burgard, Robin E. Osterhout, Stephen J. Van Dien, Cara Ann Tracewell, Priti Pharkya, Stefan Andrae
Abstract: Described herein are engineered cells including ones having synthetic methylotrophy which include an NADH-dependent enzyme capable of converting G3P to 3PG (e.g., B. methanolicus gapN) and/or fructose-1,6-bisphosphatase, along with hexulose-6-phosphate synthase, 6-phospho-3-hexuloisomerase, a phosphoketolase, or a combination thereof. Engineered cells of the disclosure beneficially maintain adequate pool sizes of phosphorylated C3 and/or C4 compounds, and/or provide increased levels of NADPH. As such, the modifications allow for the generation of C6 compounds from C1 (e.g., a methanol feedstod) and C5 compounds, the regeneration of C5 compounds from C6 compounds by carbon rearrangement, and an improved balance between regeneration of C5 compounds and lower glycolysis. In turn, this allows the engineered microorganism to generate sufficient quantities of metabolic precursors (e.g.
Type:
Grant
Filed:
June 26, 2019
Date of Patent:
February 25, 2025
Assignee:
Genomatica, Inc.
Inventors:
Harish Nagarajan, Tae Hoon Yang, Ali Khodayari
Abstract: The disclosure relates to the field of specialty chemicals and methods for their synthesis. In embodiments, the disclosure provides viable bacterial cells which comprise heterologous dual 3-hydroxy-acyl-ACP dehydratase/isomerases, etc. The disclosure further provides monounsaturated fatty acid derivative molecules produced by the viable bacterial cells which are non-native to the bacterial cells. The disclosure further provides methods for the preparation and production of non-native monounsaturated fatty acid derivative molecules such as e.g., an ?3-monounsaturated fatty acid derivative, an ?5-monounsaturated fatty acid derivative, an ?9-monounsaturated fatty acid derivative, an ?11-monounsaturated fatty acid fatty acid derivative, etc.
Type:
Grant
Filed:
August 28, 2019
Date of Patent:
February 11, 2025
Assignee:
Genomatica, Inc.
Inventors:
Andreas W. Schirmer, Katherine Ann Murphy, Erin Frances Perry