Metabolic engineering of Mannheimia succiniciproducens for succinic acid production based on elementary mode analysis with clustering

2017 ◽  
Vol 12 (2) ◽  
pp. 1600701 ◽  
Author(s):  
Won Jun Kim ◽  
Jung Ho Ahn ◽  
Hyun Uk Kim ◽  
Tae Yong Kim ◽  
Sang Yup Lee
Keyword(s):  
Metabolic Engineering ◽  
Succinic Acid ◽  
Acid Production ◽  
Mode Analysis ◽  
Elementary Mode ◽  
Elementary Mode Analysis ◽  
Mannheimia Succiniciproducens ◽  
Succinic Acid Production

From genome sequence to integrated bioprocess for succinic acid production by Mannheimia succiniciproducens

2008 ◽  
Vol 79 (1) ◽  
pp. 11-22 ◽  
Author(s):  
Sang Yup Lee ◽  
Ji Mahn Kim ◽  
Hyohak Song ◽  
Jeong Wook Lee ◽  
Tae Yong Kim ◽  
...  
Keyword(s):  
Succinic Acid ◽  
Genome Sequence ◽  
Acid Production ◽  
Mannheimia Succiniciproducens ◽  
Succinic Acid Production ◽  
Integrated Bioprocess

scholarly journals Using genome-scale model to predict the metabolic engineering impact on Escherichia coli metabolism during succinic acid production optimization

2020 ◽  
Vol 25 (3) ◽  
pp. 1666-1676
Author(s):  
ZSOLT BODOR ◽  
◽  
ANDREA (IUHÁSZ) FAZAKAS ◽  
KATALIN BODOR ◽  
ERIKA KOVÁCS ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Metabolic Engineering ◽  
Succinic Acid ◽  
Acid Production ◽  
Production Optimization ◽  
Scale Model ◽  
Succinic Acid Production ◽  
Genome Scale ◽  
Genome Scale Model

scholarly journals Metabolic Engineering of Actinobacillus succinogenes Provides Insights into Succinic Acid Biosynthesis

2017 ◽  
Vol 83 (17) ◽  
Author(s):  
Michael T. Guarnieri ◽  
Yat-Chen Chou ◽  
Davinia Salvachúa ◽  
Ali Mohagheghi ◽  
Peter C. St. John ◽  
...  
Keyword(s):  
Metabolic Engineering ◽  
Succinic Acid ◽  
Acid Production ◽  
Tca Cycle ◽  
Economic Feasibility ◽  
High Yield ◽  
Actinobacillus Succinogenes ◽  
Acid Biosynthesis ◽  
Content Type ◽  
Succinic Acid Production

ABSTRACT Actinobacillus succinogenes, a Gram-negative facultative anaerobe, exhibits the native capacity to convert pentose and hexose sugars to succinic acid (SA) with high yield as a tricarboxylic acid (TCA) cycle intermediate. In addition, A. succinogenes is capnophilic, incorporating CO2 into SA, making this organism an ideal candidate host for conversion of lignocellulosic sugars and CO2 to an emerging commodity bioproduct sourced from renewable feedstocks. In this work, we report the development of facile metabolic engineering capabilities in A. succinogenes, enabling examination of SA flux determinants via knockout of the primary competing pathways—namely, acetate and formate production—and overexpression of the key enzymes in the reductive branch of the TCA cycle leading to SA. Batch fermentation experiments with the wild-type and engineered strains using pentose-rich sugar streams demonstrate that the overexpression of the SA biosynthetic machinery (in particular, the enzyme malate dehydrogenase) enhances flux to SA. Additionally, removal of competitive carbon pathways leads to higher-purity SA but also triggers the generation of by-products not previously described from this organism (e.g., lactic acid). The resultant engineered strains also lend insight into energetic and redox balance and elucidate mechanisms governing organic acid biosynthesis in this important natural SA-producing microbe. IMPORTANCE Succinic acid production from lignocellulosic residues is a potential route for enhancing the economic feasibility of modern biorefineries. Here, we employ facile genetic tools to systematically manipulate competing acid production pathways and overexpress the succinic acid-producing machinery in Actinobacillus succinogenes. Furthermore, the resulting strains are evaluated via fermentation on relevant pentose-rich sugar streams representative of those from corn stover. Overall, this work demonstrates genetic modifications that can lead to succinic acid production improvements and identifies key flux determinants and new bottlenecks and energetic needs when removing by-product pathways in A. succinogenes metabolism.

scholarly journals Genome-Based Metabolic Engineering of Mannheimia succiniciproducens for Succinic Acid Production

2006 ◽  
Vol 72 (3) ◽  
pp. 1939-1948 ◽  
Author(s):  
Sang Jun Lee ◽  
Hyohak Song ◽  
Sang Yup Lee
Keyword(s):  
Succinic Acid ◽  
Acid Production ◽  
Gene Knockout ◽  
Product Formation ◽  
Anaerobic Growth ◽  
Fermentation Products ◽  
Acid Yield ◽  
Mannheimia Succiniciproducens ◽  
Succinic Acid Production ◽  
Pep Carboxykinase

ABSTRACT Succinic acid is a four-carbon dicarboxylic acid produced as one of the fermentation products of anaerobic metabolism. Based on the complete genome sequence of a capnophilic succinic acid-producing rumen bacterium, Mannheimia succiniciproducens, gene knockout studies were carried out to understand its anaerobic fermentative metabolism and consequently to develop a metabolically engineered strain capable of producing succinic acid without by-product formation. Among three different CO2-fixing metabolic reactions catalyzed by phosphoenolpyruvate (PEP) carboxykinase, PEP carboxylase, and malic enzyme, PEP carboxykinase was the most important for the anaerobic growth of M. succiniciproducens and succinic acid production. Oxaloacetate formed by carboxylation of PEP was found to be converted to succinic acid by three sequential reactions catalyzed by malate dehydrogenase, fumarase, and fumarate reductase. Major metabolic pathways leading to by-product formation were successfully removed by disrupting the ldhA, pflB, pta, and ackA genes. This metabolically engineered LPK7 strain was able to produce 13.4 g/liter of succinic acid from 20 g/liter glucose with little or no formation of acetic, formic, and lactic acids, resulting in a succinic acid yield of 0.97 mol succinic acid per mol glucose. Fed-batch culture of M. succiniciproducens LPK7 with intermittent glucose feeding allowed the production of 52.4 g/liter of succinic acid, with a succinic acid yield of 1.16 mol succinic acid per mol glucose and a succinic acid productivity of 1.8 g/liter/h, which should be useful for industrial production of succinic acid.

Sustainability assessment of succinic acid production technologies from biomass using metabolic engineering

2016 ◽  
Vol 9 (9) ◽  
pp. 2794-2805 ◽  
Author(s):  
Merten Morales ◽  
Meriç Ataman ◽  
Sara Badr ◽  
Sven Linster ◽  
Ioannis Kourlimpinis ◽  
...  
Keyword(s):  
Metabolic Engineering ◽  
Environmental Impact ◽  
Succinic Acid ◽  
Acid Production ◽  
Sustainability Assessment ◽  
State Of The Art ◽  
Process Modelling ◽  
Economic Feasibility ◽  
Production Technologies ◽  
Succinic Acid Production

Innovative pathways for bio-succinic acid production from biomass are investigated regarding their environmental impact, economic feasibility and process hazard by including state of the art metabolic engineering in process modelling.

Modeling of batch fermentation kinetics for succinic acid production by Mannheimia succiniciproducens

2008 ◽  
Vol 40 (1) ◽  
pp. 107-115 ◽  
Author(s):  
Hyohak Song ◽  
Seh Hee Jang ◽  
Jong Myoung Park ◽  
Sang Yup Lee
Keyword(s):  
Succinic Acid ◽  
Acid Production ◽  
Batch Fermentation ◽  
Fermentation Kinetics ◽  
Mannheimia Succiniciproducens ◽  
Succinic Acid Production

Homo-succinic acid production by metabolically engineered Mannheimia succiniciproducens

2016 ◽  
Vol 38 ◽  
pp. 409-417 ◽  
Author(s):  
Jeong Wook Lee ◽  
Jongho Yi ◽  
Tae Yong Kim ◽  
Sol Choi ◽  
Jung Ho Ahn ◽  
...  
Keyword(s):  
Succinic Acid ◽  
Acid Production ◽  
Mannheimia Succiniciproducens ◽  
Succinic Acid Production
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