skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Synthetic methylotrophy: engineering the production of biofuels and chemicals based on the biology of aerobic methanol utilization

Journal Article · · Current Opinion in Biotechnology

Synthetic methylotrophy is the development of non-native methylotrophs that can utilize methane and methanol as sole carbon and energy sources or as co-substrates with carbohydrates to produce metabolites as biofuels and chemicals. Here, the availability of methane (from natural gas) and its oxidation product, methanol, has been increasing, while prices have been decreasing, thus rendering them as attractive fermentation substrates. As they are more reduced than most carbohydrates, methane and methanol, as co-substrates, can enhance the yields of biologically produced metabolites. Here we discuss synthetic biology and metabolic engineering strategies based on the native biology of aerobic methylotrophs for developing synthetic strains grown on methanol, with Escherichia coli as the prototype.

Research Organization:
Univ. of Delaware, Newark, DE (United States)
Sponsoring Organization:
USDOE Advanced Research Projects Agency - Energy (ARPA-E)
Grant/Contract Number:
AR0000432
OSTI ID:
1749883
Journal Information:
Current Opinion in Biotechnology, Vol. 33; ISSN 0958-1669
Publisher:
ElsevierCopyright Statement
Country of Publication:
United States
Language:
English

References (46)

The significance of regulation and land use patterns on natural gas resource estimates in the Marcellus shale journal November 2012
Rethinking biological activation of methane and conversion to liquid fuels journal April 2014
Bioconversion of natural gas to liquid fuel: Opportunities and challenges journal May 2014
Methanol utilization by a novel thermophilic homoacetogenic bacterium, Moorella mulderi sp. nov., isolated from a bioreactor journal March 2003
The Biochemistry of Methane Oxidation journal June 2007
Methylotrophic Bacillus methanolicus Encodes Two Chromosomal and One Plasmid Born NAD+ Dependent Methanol Dehydrogenase Paralogs with Different Catalytic and Biochemical Properties journal March 2013
Yeast Methylotrophy: Metabolism, Gene Regulation and Peroxisome Homeostasis journal January 2011
Characterization of a Novel Methanol Dehydrogenase in Representatives of Burkholderiales: Implications for Environmental Detection of Methylotrophy and Evidence for Convergent Evolution journal April 2008
Escherichia coli is unable to produce pyrroloquinoline quinone (PQQ) journal October 1997
The pyrroloquinoline quinone biosynthesis pathway revisited: A structural approach journal January 2008
Synthesis of pyrroloquinoline quinone in vivo and in vitro and detection of an intermediate in the biosynthetic pathway. journal September 1995
A new alcohol dehydrogenase, reactive towards methanol, from Bacillus stearothermophilus journal June 1988
The Physiological Role of the Ribulose Monophosphate Pathway in Bacteria and Archaea journal January 2006
Genomic organization and biochemistry of the ribulose monophosphate pathway and its application in biotechnology journal July 2009
Genome of Methylobacillus flagellatus, Molecular Basis for Obligate Methylotrophy, and Polyphyletic Origin of Methylotrophy journal April 2007
The gene encoding the ribulose monophosphate pathway enzyme, 3-hexulose-6-phosphate synthase, from Aminomonas aminovorus C2A1 is adjacent to coding sequences that exhibit similarity to histidine biosynthesis enzymes. journal August 2004
A Novel Operon Encoding Formaldehyde Fixation: the Ribulose Monophosphate Pathway in the Gram-Positive Facultative Methylotrophic Bacterium Mycobacterium gastri MB19 journal February 2000
Plasmid-Dependent Methylotrophy in Thermotolerant Bacillus methanolicus journal February 2004
Upregulated Transcription of Plasmid and Chromosomal Ribulose Monophosphate Pathway Genes Is Critical for Methanol Assimilation Rate and Methanol Tolerance in the Methylotrophic Bacterium Bacillus methanolicus journal April 2006
Proteomic analysis of the thermophilic methylotroph Bacillus methanolicus MGA3 journal February 2014
Characterization of two transketolases encoded on the chromosome and the plasmid pBM19 of the facultative ribulose monophosphate cycle methylotroph Bacillus methanolicus journal January 2014
Characterization of Fructose 1,6-Bisphosphatase and Sedoheptulose 1,7-Bisphosphatase from the Facultative Ribulose Monophosphate Cycle Methylotroph Bacillus methanolicus journal September 2013
The methylotrophic Bacillus methanolicus MGA3 possesses two distinct fructose 1,6-bisphosphate aldolases journal August 2013
Bifunctional enzyme fusion of 3-hexulose-6-phosphate synthase and 6-phospho-3-hexuloisomerase journal May 2007
C1 compounds as auxiliary substrate for engineered Pseudomonas putida S12 journal June 2009
Formaldehyde Fixation Contributes to Detoxification for Growth of a Nonmethylotroph, Burkholderia cepacia TM1, on Vanillic Acid journal October 2003
Assimilation, dissimilation, and detoxification of formaldehyde, a central metabolic intermediate of methylotrophic metabolism journal January 2005
Purification, characterization, and partial sequence of the glutathione-dependent formaldehyde dehydrogenase from Escherichia coli: a class III alcohol dehydrogenase journal January 1992
Global Transcriptional Effects of a Suppressor tRNA and the Inactivation of the Regulator frmR journal October 2004
Stoichiometric and energetic analyses of non-photosynthetic CO2-fixation pathways to support synthetic biology strategies for production of fuels and chemicals journal November 2012
Equations and calculations for fermentations of butyric acid bacteria journal February 1984
Engineered ketol-acid reductoisomerase and alcohol dehydrogenase enable anaerobic 2-methylpropan-1-ol production at theoretical yield in Escherichia coli journal May 2011
Construction of DNA-Shuffled and Incrementally Truncated Libraries by a Mutagenic and Unidirectional Reassembly Method: Changing from a Substrate Specificity of Phospholipase to That of Lipase journal December 2002
Expressed Genome of Methylobacillus flagellatus as Defined through Comprehensive Proteomics and New Insights into Methylotrophy journal July 2010
Genome sequence and analysis of methylotrophic yeast Hansenula polymorpha DL1 journal January 2013
Adaptation of Hansenula polymorpha to methanol: a transcriptome analysis journal January 2010
Responses of the Central Metabolism in Escherichia coli to Phosphoglucose Isomerase and Glucose-6-Phosphate Dehydrogenase Knockouts journal December 2003
Global metabolic response of Escherichia coli to gnd or zwf gene-knockout, based on 13 C-labeling experiments and the measurement of enzyme activities journal March 2004
Engineering the pentose phosphate pathway to improve hydrogen yield in recombinant Escherichia coli journal July 2011
A study of methanol transport/uptake by a methanol-utilizing bacteriumL3 in a batch bioreactor journal January 1989
Role of formaldehyde in the utilization of C1 compounds via the ribulose monophosphate cycle journal March 1978
Absolute metabolite concentrations and implied enzyme active site occupancy in Escherichia coli journal June 2009
Real-time determination of intracellular oxygen in bacteria using a genetically encoded FRET-based biosensor journal January 2012
Comparative toxicity of hydrogen peroxide, hydroxyl radicals, and superoxide anion to Escherichia coli journal June 2003
Catalytic mechanism of quinoprotein methanol dehydrogenase: A theoretical and x-ray crystallographic investigation journal January 2001
Determination of enzyme mechanisms by molecular dynamics: Studies on quinoproteins, methanol dehydrogenase, and soluble glucose dehydrogenase journal August 2004

Cited By (30)

Metabolic engineering of methanotrophs and its application to production of chemicals and biofuels from methane: Biofuel energy consumption-Economic growth relationship: An empirical investigation of Brazil journal August 2016
Methanol as carbon substrate in the bio‐economy: Metabolic engineering of aerobic methylotrophic bacteria for production of value‐added chemicals journal May 2017
Development of a formaldehyde biosensor with application to synthetic methylotrophy journal November 2017
Engineering Artificial Fusion Proteins for Enhanced Methanol Bioconversion journal October 2018
Synthetic Methylotrophy: Past, Present, and Future book January 2018
Production of carbon-13-labeled cadaverine by engineered Corynebacterium glutamicum using carbon-13-labeled methanol as co-substrate journal August 2015
Characterization and evolution of an activator-independent methanol dehydrogenase from Cupriavidus necator N-1 journal February 2016
Biological conversion of methane to chemicals and fuels: technical challenges and issues journal February 2018
Growth of Bacillus methanolicus in 2 M methanol at 50 °C: the effect of high methanol concentration on gene regulation of enzymes involved in formaldehyde detoxification by the ribulose monophosphate pathway journal May 2015
Comparison of the Wild-Type Obligate Methylotrophic Bacterium Methylophilus quaylei and its Isogenic Streptomycin-Resistant Mutant via Metal Nanoparticle Generation journal May 2019
Reconstruction of methanol and formate metabolic pathway in non-native host for biosynthesis of chemicals and biofuels journal August 2016
Harnessing the power of microbial autotrophy journal September 2016
A semi-synthetic regulon enables rapid growth of yeast on xylose journal March 2018
Methanol-essential growth of Escherichia coli journal April 2018
Improving formaldehyde consumption drives methanol assimilation in engineered E. coli journal June 2018
Barriers and opportunities in bio-based production of hydrocarbons journal July 2018
Guidance for engineering of synthetic methylotrophy based on methanol metabolism in methylotrophy journal January 2017
Scaffoldless engineered enzyme assembly for enhanced methanol utilization journal October 2016
Thermophilic methanotrophs: in hot pursuit journal August 2019
Microbial microdroplet culture system (MMC): an integrated platform for automated, high–throughput microbial cultivation and adaptive evolution journal December 2019
Methanol fermentation increases the production of NAD(P)H-dependent chemicals in synthetic methylotrophic Escherichia coli journal January 2019
Biological conversion of methanol by evolved Escherichia coli carrying a linear methanol assimilation pathway journal September 2017
Improved methanol-derived lovastatin production through enhancement of the biosynthetic pathway and intracellular lovastatin efflux in methylotrophic yeast journal May 2018
Evaluation of synthetic formaldehyde and methanol assimilation pathways in Yarrowia lipolytica journal December 2019
Palladium Nanoparticles: Toxicological Effects and Potential Implications for Occupational Risk Assessment journal February 2018
Microbial microdroplet culture system (MMC): An integrated platform for automated, high‐throughput microbial cultivation and adaptive evolution journal April 2020
Methanol-essential growth of Escherichia coli text January 2018
Sugar Synthesis from CO2 in Escherichia coli journal June 2016
Sort-Seq Approach to Engineering a Formaldehyde-Inducible Promoter for Dynamically Regulated Escherichia coli Growth on Methanol journal May 2017
Phage-Assisted Evolution of Bacillus methanolicus Methanol Dehydrogenase 2 journal March 2019