@article{zeldes_loder_counts_haque_widney_keller_albers_kelly_2019, title={Determinants of sulphur chemolithoautotrophy in the extremely thermoacidophilic Sulfolobales}, volume={21}, ISSN={["1462-2920"]}, DOI={10.1111/1462-2920.14712}, abstractNote={Summary}, number={10}, journal={ENVIRONMENTAL MICROBIOLOGY}, author={Zeldes, Benjamin M. and Loder, Andrew J. and Counts, James A. and Haque, Mashkurul and Widney, Karl A. and Keller, Lisa M. and Albers, Sonja-Verena and Kelly, Robert M.}, year={2019}, month={Oct}, pages={3696–3710} }
 @article{khatibi_chou_loder_zurawski_adams_kelly_2017, title={Impact of growth mode, phase, and rate on the metabolic state of the extremely thermophilic archaeon Pyrococcus furiosus}, volume={114}, ISSN={["1097-0290"]}, DOI={10.1002/bit.26408}, abstractNote={Abstract}, number={12}, journal={BIOTECHNOLOGY AND BIOENGINEERING}, author={Khatibi, Piyum A. and Chou, Chung-jung and Loder, Andrew J. and Zurawski, Jeffrey V. and Adams, Michael W. W. and Kelly, Robert M.}, year={2017}, month={Dec}, pages={2947–2954} }
 @article{lian_zeldes_lipscomb_hawkins_han_loder_nishiyama_adams_kelly_2016, title={Ancillary contributions of heterologous biotin protein ligase and carbonic anhydrase for CO2 incorporation into 3-hydroxypropionate by metabolically engineered Pyrococcus furiosus}, volume={113}, number={12}, journal={Biotechnology and Bioengineering}, author={Lian, H. and Zeldes, B. M. and Lipscomb, G. L. and Hawkins, A. B. and Han, Y. J. and Loder, A. J. and Nishiyama, D. and Adams, M. W. W. and Kelly, R. M.}, year={2016}, pages={2652–2660} }
 @article{loder_han_hawkins_lian_lipscomb_schut_keller_adams_kelly_2016, title={Reaction kinetic analysis of the 3-hydroxypropionate/4-hydroxybutyrate CO2 fixation cycle in extremely thermoacidophilic archaea}, volume={38}, ISSN={["1096-7184"]}, DOI={10.1016/j.ymben.2016.10.009}, abstractNote={The 3-hydroxypropionate/4-hydroxybutyrate (3HP/4HB) cycle fixes CO2 in extremely thermoacidophilic archaea and holds promise for metabolic engineering because of its thermostability and potentially rapid pathway kinetics. A reaction kinetics model was developed to examine the biological and biotechnological attributes of the 3HP/4HB cycle as it operates in Metallosphaera sedula, based on previous information as well as on kinetic parameters determined here for recombinant versions of five of the cycle enzymes (malonyl-CoA/succinyl-CoA reductase, 3-hydroxypropionyl-CoA synthetase, 3-hydroxypropionyl-CoA dehydratase, acryloyl-CoA reductase, and succinic semialdehyde reductase). The model correctly predicted previously observed features of the cycle: the 35–65% split of carbon flux through the acetyl-CoA and succinate branches, the high abundance and relative ratio of acetyl-CoA/propionyl-CoA carboxylase (ACC) and MCR, and the significance of ACC and hydroxybutyryl-CoA synthetase (HBCS) as regulated control points for the cycle. The model was then used to assess metabolic engineering strategies for incorporating CO2 into chemical intermediates and products of biotechnological importance: acetyl-CoA, succinate, and 3-hydroxypropionate.}, journal={METABOLIC ENGINEERING}, author={Loder, Andrew J. and Han, Yejun and Hawkins, Aaron B. and Lian, Hong and Lipscomb, Gina L. and Schut, Gerrit J. and Keller, Matthew W. and Adams, Michael W. W. and Kelly, Robert M.}, year={2016}, month={Nov}, pages={446–463} }
 @article{keller_lipscomb_loder_schut_kelly_adams_2015, title={A hybrid synthetic pathway for butanol production by a hyperthermophilic microbe}, volume={27}, ISSN={["1096-7184"]}, DOI={10.1016/j.ymben.2014.11.004}, abstractNote={Biologically produced alcohols are of great current interest for renewable solvents and liquid transportation fuels. While bioethanol is now produced on a massive scale, butanol has superior fuel characteristics and an additional value as a solvent and chemical feedstock. Butanol production has been demonstrated at ambient temperatures in metabolically-engineered mesophilic organisms, but the ability to engineer a microbe for in vivo high-temperature production of commodity chemicals has several distinct advantages. These include reduced contamination risk, facilitated removal of volatile products, and a wide temperature range to modulate and balance both the engineered pathway and the host׳s metabolism. We describe a synthetic metabolic pathway assembled from genes obtained from three different sources for conversion of acetyl-CoA to 1-butanol, and 1-butanol generation from glucose was demonstrated near 70°C in a microorganism that grows optimally near 100°C. The module could also be used in thermophiles capable of degrading plant biomass.}, journal={METABOLIC ENGINEERING}, author={Keller, Matthew W. and Lipscomb, Gina L. and Loder, Andrew J. and Schut, Gerrit J. and Kelly, Robert M. and Adams, Michael W. W.}, year={2015}, month={Jan}, pages={101–106} }
 @article{lewis_notey_chandrayan_loder_lipscomb_adams_kelly_2015, title={A mutant ('lab strain') of the hyperthermophilic archaeon Pyrococcus furiosus, lacking flagella, has unusual growth physiology}, volume={19}, ISSN={["1433-4909"]}, DOI={10.1007/s00792-014-0712-3}, abstractNote={A mutant ('lab strain') of the hyperthermophilic archaeon Pyrococcus furiosus DSM3638 exhibited an extended exponential phase and atypical cell aggregation behavior. Genomic DNA from the mutant culture was sequenced and compared to wild-type (WT) DSM3638, revealing 145 genes with one or more insertions, deletions, or substitutions (12 silent, 33 amino acid substitutions, and 100 frame shifts). Approximately, half of the mutated genes were transposases or hypothetical proteins. The WT transcriptome revealed numerous changes in amino acid and pyrimidine biosynthesis pathways coincidental with growth phase transitions, unlike the mutant whose transcriptome reflected the observed prolonged exponential phase. Targeted gene deletions, based on frame-shifted ORFs in the mutant genome, in a genetically tractable strain of P. furiosus (COM1) could not generate the extended exponential phase behavior observed for the mutant. For example, a putative radical SAM family protein (PF2064) was the most highly up-regulated ORF (>25-fold) in the WT between exponential and stationary phase, although this ORF was unresponsive in the mutant; deletion of this gene in P. furiosus COM1 resulted in no apparent phenotype. On the other hand, frame-shifting mutations in the mutant genome negatively impacted transcription of a flagellar biosynthesis operon (PF0329-PF0338).Consequently, cells in the mutant culture lacked flagella and, unlike the WT, showed minimal evidence of exopolysaccharide-based cell aggregation in post-exponential phase. Electron microscopy of PF0331-PF0337 deletions in P. furiosus COM1 showed that absence of flagella impacted normal cell aggregation behavior and, furthermore, indicated that flagella play a key role, beyond motility, in the growth physiology of P. furiosus.}, number={2}, journal={EXTREMOPHILES}, author={Lewis, Derrick L. and Notey, Jaspreet S. and Chandrayan, Sanjeev K. and Loder, Andrew J. and Lipscomb, Gina L. and Adams, Michael W. W. and Kelly, Robert M.}, year={2015}, month={Mar}, pages={269–281} }
 @article{loder_zeldes_garrison_lipscomb_adams_kelly_2015, title={Alcohol Selectivity in a Synthetic Thermophilic n-Butanol Pathway Is Driven by Biocatalytic and Thermostability Characteristics of Constituent Enzymes}, volume={81}, ISSN={["1098-5336"]}, DOI={10.1128/aem.02028-15}, abstractNote={ABSTRACT}, number={20}, journal={APPLIED AND ENVIRONMENTAL MICROBIOLOGY}, author={Loder, Andrew J. and Zeldes, Benjamin M. and Garrison, G. Dale, II and Lipscomb, Gina L. and Adams, Michael W. W. and Kelly, Robert M.}, year={2015}, month={Oct}, pages={7187–7200} }
 @article{hawkins_lian_zeldes_loder_lipscomb_schut_keller_adams_kelly_2015, title={Bioprocessing analysis of Pyrococcus furiosus strains engineered for CO2-based 3-hydroxypropionate production}, volume={112}, ISSN={["1097-0290"]}, DOI={10.1002/bit.25584}, abstractNote={ABSTRACT}, number={8}, journal={BIOTECHNOLOGY AND BIOENGINEERING}, author={Hawkins, Aaron B. and Lian, Hong and Zeldes, Benjamin M. and Loder, Andrew J. and Lipscomb, Gina L. and Schut, Gerrit J. and Keller, Matthew W. and Adams, Michael W. W. and Kelly, Robert M.}, year={2015}, month={Aug}, pages={1533–1543} }
 @misc{zeldes_keller_loder_straub_adams_kelly_2015, title={Extremely thermophilic microorganisms as metabolic engineering platforms for production of fuels and industrial chemicals}, volume={6}, ISSN={["1664-302X"]}, DOI={10.3389/fmicb.2015.01209}, abstractNote={Enzymes from extremely thermophilic microorganisms have been of technological interest for some time because of their ability to catalyze reactions of industrial significance at elevated temperatures. Thermophilic enzymes are now routinely produced in recombinant mesophilic hosts for use as discrete biocatalysts. Genome and metagenome sequence data for extreme thermophiles provide useful information for putative biocatalysts for a wide range of biotransformations, albeit involving at most a few enzymatic steps. However, in the past several years, unprecedented progress has been made in establishing molecular genetics tools for extreme thermophiles to the point that the use of these microorganisms as metabolic engineering platforms has become possible. While in its early days, complex metabolic pathways have been altered or engineered into recombinant extreme thermophiles, such that the production of fuels and chemicals at elevated temperatures has become possible. Not only does this expand the thermal range for industrial biotechnology, it also potentially provides biodiverse options for specific biotransformations unique to these microorganisms. The list of extreme thermophiles growing optimally between 70 and 100°C with genetic toolkits currently available includes archaea and bacteria, aerobes and anaerobes, coming from genera such as Caldicellulosiruptor, Sulfolobus, Thermotoga, Thermococcus, and Pyrococcus. These organisms exhibit unusual and potentially useful native metabolic capabilities, including cellulose degradation, metal solubilization, and RuBisCO-free carbon fixation. Those looking to design a thermal bioprocess now have a host of potential candidates to choose from, each with its own advantages and challenges that will influence its appropriateness for specific applications. Here, the issues and opportunities for extremely thermophilic metabolic engineering platforms are considered with an eye toward potential technological advantages for high temperature industrial biotechnology.}, journal={FRONTIERS IN MICROBIOLOGY}, author={Zeldes, Benjamin M. and Keller, Matthew W. and Loder, Andrew J. and Straub, Christopher T. and Adams, Michael W. W. and Kelly, Robert M.}, year={2015}, month={Nov} }