renewable biochemicals for a sustainable future

Enhancing biofuel production (Example)

Release intrinsic genetic and biochemical constraints limiting renewable fuels and chemicals production

The native regulatory mechanisms at the transcriptional and biochemical levels to maintain cellular homeostasis often limit hyperproduction of fermentation products, especially for nonnative products. We aim to characterize these regulatory mechanisms and release these constraints.

Characterizing export systems (Example)

Characterize and optimize transport and efflux systems across cell membranes to enhance production and cellular robustness

Cellular transport across the cytoplasmic membrane for substrate import and product export represents potential bottlenecks for bioproduction, thus providing us an interesting research topic.

Engineering synthetic cocultures (Example)

Develop new engineering strategies for value-added chemical production

We are interested in developing new engineering strategies such as synthetic cocultures and novel genome engineering tools.

Publications@ASU

2023

Godar, A., Chase, T., Conway, D., Ravichandran, D., Woodson, I., Lai, Y., Song, K., Rittmann, B., Wang, X., Nielsen, D. (2023) ‘Dark’ CO2 fixation in succinate fermentations enabled by direct CO2 delivery via hollow fiber membrane carbonation. Bioprocess and Biosystems Engineering https://link.springer.com/article/10.1007/s00449-023-02957-3

We successfully used hollow fiber membrane to deliver CO2 to cells to fix inorganic carbons into succinate.

Liu, A., Machas, M., Mhatre, A., Hajinajaf, N., Sarnaik, A., Nichols, N., Frazer, S., Wang, X., Varman, A., Nielsen, D. (2023) Synergistic co‐utilization of biomass‐derived sugars enhances aromatic amino acid production by engineered Escherichia coli. Biotechnol Bioeng. https://doi.org/10.1002/bit.28585

Dr. Nielsen's and Dr. Varmen's teams used XylR* to enhance sugar aerobic coutilization to produce amino acids.

2022

Mhatre, A., Kalscheur, B., Mckeown, H., Bhakta, K., Sarnaik, A., Flores, A., Nielsen, D., Wang, X., Soundappan, T., Varman A. (2022) Consolidated bioprocessing of hemicellulose to fuels and chemicals through an engineered Bacillus subtilis-Escherichia coli consortium https://www.sciencedirect.com/science/article/pii/S0960148122005924

We helped Dr. Varman's team to build a coculture to convert hemicellulose to fuels and chemicals.

Kurgan, G., Onyeabor, M., Holland, S., Taylor, E., Schneider, A., Kurgan, L., Billings, T., Wang, X. (2022) Directed evolution of Zymomonas mobilis sugar facilitator Glf to overcome glucose inhibition. J Ind Microbiol Biotechnol. https://doi.org/10.1093/jimb/kuab066

Through directed evolution, the mutations in Z. mobilis sugar facilitator Glf such as A165Mbvand L445I were discovered to released glucose inhibition.

2021

Godar, A., Kamoku, C., Nielsen, D., Wang, X. (2021) Synthetic biology strategies to address waste CO2 loss during biofuel production. Curr Opin Environ Sci Health. https://doi.org/10.1016/j.coesh.2021.100305

We reviewed synthetic biology strategies to conserve/capture CO2 emission during biofuel production.

Flores, A., Holland, S., Mhatre, A., Sarnaik, A., Godar, A., Onyeabor, M., Varman A., Wang, X.* and Nielsen, D.* (2021) A coculture-coproduction system designed for enhanced carbon conservation through inter-strain CO2 recycling. Metab Eng. https://doi:10.1016/j.ymben.2021.08.001

We constructed a synthetic coculture-coproduction system for direct CO2-recycling. Tracking chemical details of CO2 fixation by PEP carboxylation revealed unexpected carbon exchange between two strains.

Machas, M., Kurgan, G., Abed, O.A., Shapiro, A., Wang, X. and Nielsen, D. (2021) Characterizing Escherichia coli's transcriptional response to different styrene exposure modes reveals novel toxicity and tolerance insights. J Ind Microbiol Biotechnol. doi:10.1093/jimb/kuab019

We investigated the E. coli's transcriptional responses to styrene external exposure and internal production.

2020

Flores, A., Choi, H., Martinez, R., Onyeabor, M., Ayla EZ., Godar, A., Machas, M., Nielsen, D. and Wang, X. (2020) Catabolic Division of Labor Enhances Production of D-Lactate and Succinate From Glucose-Xylose Mixtures in Engineered Escherichia coli Co-culture Systems. Front Bioeng Biotechnol. 8:329. DOI:10.3389/fbioe.2020.00329

To further test our strategy of synthetic coculture engieering for glucose-xylose fermentation, we successfully developed E. coli binary cocultures to efficiently convert sugar mixtures into lactate and succinate.

Onyeabor, M., Martinez, R., Kurgan, G.and Wang, X. (2020) Engineering transport systems for microbial production. Adv Appl Microbiol DOI:10.1016/bs.aambs.2020.01.002

We comprehensively reviewed the transport systems critical for microbial production as well as current genetic engineering strategies to improve transport functions and thus production metrics.

2019

Kurgan, G., Kurgan, L., Schneider, A., Onyeabor, M., Rodriguez-Sanchez, Y., Taylor, E., Carbonell, P., Martinez, R., Shi, X., Gu, H. and Wang, X. (2019) Identification of major malate export systems in an engineered malate producing Escherichia coli aided by substrate similarity search. Appl Microbiol Biotechnol. doi: 10.1007/s00253-019-10164-y.

We found that DcuA, CitT, and TtdT consitute the major malate export system in E. coli using a cheminformatics-guided genetic approach.

Martinez, R., Flores, A., Dufault, M., Wang, X. (2019) The XylR variant (R121C and P363S) releases arabinose‐induced catabolite repression on xylose fermentation and enhances coutilization of lignocellulosic sugar mixtures. Biotechnol Bioeng. doi:10.1002/bit.27144

We discovered that chromosomal integration of xylR* (R121C and P363S) releases L-arabinose-induced repression and enhances co-fermentation of lignocellulosic sugar mixtures. As shown in the figure, the xylR* integration enabled ethanologenic E. coli LY180 to achieve a full coutilization of 120 g/L glucose-xylose-arabinose sugar mixtures.

Kurgan, G., Sievert, C., Flores, A., Schneider, A., Billings, T., Panyon, L., Morris, C., Taylor, E., Kurgan, L., Cartwright, R., Wang, X. (2019) Parallel experimental evolution reveals a novel repressive control of GalP on xylose fermentation in Escherichia coli. Biotechnol Bioeng. doi:10.1002/bit.27004

We discovered that a commonly used substitute glucose transporter, GalP, represses the catabolism of secondary sugars, such as xylose, in E. coli by transcriptionally downregulating the relevant catabolic genes.

Flores, A., Zeynep, A., Nielsen, D., Wang, X. (2019) Engineering a synthetic, catabolically orthogonal coculture system for enhanced conversion of lignocellulose-derived sugars to ethanol. ACS Synth Biol. doi:10.1021/acssynbio.9b00007

We engineered a series of synthetic, catabolically-orthogonal co-culture systems and developed a tuning strategy to easily balance the catabolic activities in the synthetic communities.

Flores, A., Wang, X., Nielsen, D. (2019) Recent trends in integrated bioprocesses: aiding and expanding microbial biofuel/biochemical production. Curr Opin Biotechnol. 57, 82-87

We comprehensively reviewed the recent progress about the integrated bioprocesses for fuels and chemicals production.

Kurgan, G., Panyon, L., Rodriguez-Sanchez, Y., Pacheco, E., Nieves, L. M., Mann, R., Nielsen, D., Wang, X. (2019). Bioprospecting of native efflux pumps to enhance furfural tolerance in ethanologenic Escherichia coli. Appl Environ Microbiol. 85:e02985-18

We screened all native multidrug pumps in E. coli and found small multidrug resistance (SMR) pumps conferring furfural tolerance.

2018

Machas, M., Kurgan, G., Flores, A., Schneider, A., Jha, A., Coyle, S., Varman, A., Wang, X., and Nielsen, D. (2018). Emerging tools, enabling technologies, and future opportunities for the bioproduction of aromatic chemicals. J Chem Technol Biotechnol. doi:10.1002/jctb.5762

We reviewed the challenges and opportunities for aromatics bioproduction.

2017

Sievert, C., Nieves, L. M., Panyon, L. A., Loeffler, T., Morris, C., Cartwright, R., Wang, X. (2017) Experimental evolution reveals a novel avenue to release catabolite repression via mutations in XylR. Proc Natl Acad Sci U S A. 114, 7349-7354

In this work, we discovered an effective, simple and universal genetic method to enhance sugar co-utilization in E. coli. In the News: Chem Euro, Science Daily, Eurek Alert!, etc.

2016

Flores, A., Kurgan, G., Wang, X. (2016). Engineering bacterial sugar catabolism and tolerance toward lignocellulose conversion. Chapter Six in Engineering of Microorganisms for the Production of Chemicals and Biofuels from Renewable Resources. G. Gosset ed. (Springer) ISBN 9783319517285 pp. 147-180

2015

Nieves, L.M., Panyon, L.A., Wang, X. (2015) Engineering sugar utilization and microbial tolerance toward lignocellulose conversion. Front Bioeng Biotechnol. DOI: 10.3389/fbioe.2015.00017.

In this review, we discussed the current major challenges for lignocellulose bioconversion.

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