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Title: Elimination of metabolic pathways to all traditional fermentation products increases ethanol yields in Clostridium thermocellum

Journal Article · · Metabolic Engineering
 [1];  [2];  [2];  [1]
  1. Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Univ. of Tennessee, Knoxville, TN (United States)
  2. Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

Clostridium thermocellum has the natural ability to convert cellulose to ethanol, making it a promising candidate for consolidated bioprocessing (CBP) of cellulosic biomass to biofuels. To further improve its CBP capabilities, we study a mutant strain of C. thermocellum that was constructed (strain AG553; C. thermocellum Δhpt ΔhydG Δldh Δpfl Δpta-ack) to increase flux to ethanol by removing side product formation. Strain AG553 showed a two- to threefold increase in ethanol yield relative to the wild type on all substrates tested. On defined medium, strain AG553 exceeded 70% of theoretical ethanol yield on lower loadings of the model crystalline cellulose Avicel, effectively eliminating formate, acetate, and lactate production and reducing H2 production by fivefold. On 5 g/L Avicel, strain AG553 reached an ethanol yield of 63.5% of the theoretical maximum compared with 19.9% by the wild type, and it showed similar yields on pretreated switchgrass and poplar. The elimination of organic acid production suggested that the strain might be capable of growth under higher substrate loadings in the absence of pH control. Final ethanol titer peaked at 73.4 mM in mutant AG553 on 20 g/L Avicel, at which point the pH decreased to a level that does not allow growth of C. thermocellum, likely due to CO2 accumulation. In comparison, the maximum titer of wild type C. thermocellum was 14.1 mM ethanol on 10 g/L Avicel. In conclusion, with the elimination of the metabolic pathways to all traditional fermentation products other than ethanol, AG553 is the best ethanol-yielding CBP strain to date and will serve as a platform strain for further metabolic engineering for the bioconversion of lignocellulosic biomass.

Research Organization:
Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States). BioEnergy Science Center (BESC)
Sponsoring Organization:
USDOE Office of Science (SC)
Grant/Contract Number:
AC05-00OR22725
OSTI ID:
1286864
Alternate ID(s):
OSTI ID: 1250941
Journal Information:
Metabolic Engineering, Vol. 32; ISSN 1096-7176
Publisher:
ElsevierCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 59 works
Citation information provided by
Web of Science

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Cellulosomes: bacterial nanomachines for dismantling plant polysaccharides journal December 2016
Consolidated bioprocessing of Populus using Clostridium (Ruminiclostridium) thermocellum: a case study on the impact of lignin composition and structure journal February 2016
Simultaneous achievement of high ethanol yield and titer in Clostridium thermocellum journal June 2016
Enhanced ethanol formation by Clostridium thermocellum via pyruvate decarboxylase journal October 2017
Clostridium thermocellum LL1210 pH homeostasis mechanisms informed by transcriptomics and metabolomics journal April 2018
Engineering Clostridium for improved solvent production: recent progress and perspective journal May 2019
Integrated omics analyses reveal the details of metabolic adaptation of Clostridium thermocellum to lignocellulose-derived growth inhibitors released during the deconstruction of switchgrass journal January 2017
Challenges and Advances for Genetic Engineering of Non-model Bacteria and Uses in Consolidated Bioprocessing journal October 2017
Metabolome analysis reveals a role for glyceraldehyde 3-phosphate dehydrogenase in the inhibition of C. thermocellum by ethanol journal November 2017
Engineering microbes for direct fermentation of cellulose to bioethanol journal February 2018
Expression of adhA from different organisms in Clostridium thermocellum journal November 2017
Fuelling the future: microbial engineering for the production of sustainable biofuels journal March 2016
Expression of a heat-stable NADPH-dependent alcohol dehydrogenase from Thermoanaerobacter pseudethanolicus 39E in Clostridium thermocellum 1313 results in increased hydroxymethylfurfural resistance journal March 2017
CRISPR interference (CRISPRi) as transcriptional repression tool for Hungateiclostridium thermocellum DSM 1313 journal August 2019
Evolutionary engineering of Geobacillus thermoglucosidasius for improved ethanol production : Evolutionary Engineering of journal April 2016
Overflow metabolism and growth cessation in Clostridium thermocellum DSM1313 during high cellulose loading fermentations : Overflow Metabolism and Growth Cessation in journal August 2017
Metabolic and evolutionary responses of Clostridium thermocellum to genetic interventions aimed at improving ethanol production journal March 2020
Development of a shuttle plasmid without host restriction sites for efficient transformation and heterologous gene expression in Clostridium cellulovorans journal May 2019
Improved growth rate in Clostridium thermocellum hydrogenase mutant via perturbed sulfur metabolism journal January 2017
Rational development of transformation in Clostridium thermocellum ATCC 27405 via complete methylome analysis and evasion of native restriction–modification systems journal July 2019
Nicotinamide cofactor ratios in engineered strains of Clostridium thermocellum and Thermoanaerobacterium saccharolyticum journal April 2016
Exploring complex cellular phenotypes and model-guided strain design with a novel genome-scale metabolic model of Clostridium thermocellum DSM 1313 implementing an adjustable cellulosome journal September 2016
Agronomic performance of Populus deltoides trees engineered for biofuel production journal November 2017
Holistic bioengineering: Rewiring central metabolism for enhanced bioproduction text January 2017
Promiscuous plasmid replication in thermophiles: Use of a novel hyperthermophilic replicon for genetic manipulation of Clostridium thermocellum at its optimum growth temperature journal December 2016
Progress in understanding and overcoming biomass recalcitrance: a BioEnergy Science Center (BESC) perspective journal November 2017