Fuzhong Zhang, PhD

Associate Professor
Energy, Environmental & Chemical Engineering

Plant and Microbial Biosciences Program
Molecular Microbiology and Microbial Pathogenesis Program
Computational and Systems Biology Program
Biochemistry, Biophysics, and Structural Biology Program

  • 314-935-7671

  • 314-935-7985

  • 314-935-7211

  • Brauer Hall 1022

  • fzhang29@wustl.edu

  • https://sites.wustl.edu/fuzhongzhanglab/home/

  • Synthetic biology, Metabolic engineering, regulatory systems, biofuels, biomaterials

  • Synthetic biology for advanced biofuels, biomaterials, and chemicals.

Research Abstract:

Our research focuses on engineering microbial cell-based systems to perform complex tasks and to produce renewable fuels, chemicals, and advanced materials.

Metabolite Dynamics and Heterogeneity:
Nature uses a suite of delicate regulatory systems to control both gene expression and pathway flux in response to environmental signals. When engineering microbial cells to produce fuels, chemicals, and materials, it is important to rewire the natural regulatory network, which was evolved for cell growth and replication, but not to over-produce any target compound. We are interested in developing tools to dissect the complex regulatory network of natural systems and to design synthetic regulatory systems that allow cell to control engineered pathways dynamically (Fig left). In addition, non-genetic, cell-to-cell variations in protein and metabolite concentrations cause large heterogeneity in single cell biosynthetic performance and dramatically affect ensemble product yields and titers (Fig right). We are interested in understanding the origin of metabolic noise and developing tools to regulate metabolic variation.

Advanced Biomaterials:
Most synthetic polymers are currently derived from petroleum. Increasing concerns over petroleum’s environmental impacts and declining supply demand the development of state-of-the-art technologies to manufacture polymers from renewable feedstocks. On the other hand, nature has evolved various types of materials with delicate nano-scale structural that endow desirable material properties at the macro-scale. We are interested in developing synthetic biology platforms to largely expand the synthetic power, producing high-performance materials with properties beyond their natural counterparts or with novel functions, enabling applications (sensing, protection, scaffolding, catalysis, etc.) not possible with existing materials. Published examples include microbially produced spider silk fibers that are as strong and tough as natural spider silk and mussel foot proteins (Mfps) with higher underwater adhesivity than natural Mfps.

Selected Publications:

Bowen C.H., Sargent C.J., Wang A., Zhu Y., Li J., Chang X., Mu X., Galazka J.M., Jun Y., Keten S., Zhang F.* Microbial Production of Megadalton Titin Yields Fibers with Advantageous Mechanical Properties. Nature Communications, 12, 5182, (2021)

Kim E., Jeon J., Zhu Y., Hoppe E.D., Jun Y., Genin G.M., Zhang F.* A Biosynthetic Hybrid Spidroin-Amyloid-Mussel-Foot Protein for Underwater Adhesion on Diverse Surfaces. ACS Appl. Mater. Interfaces, 13, 41, 48457–48468.(2021)

Han Y., Zhang F.,* Heterogeneity coordinates bacterial multitasking in single cells. PLoS Comput Biol. 16(1):e1007643. (2020)

Bai W., Sargent C.J., Choi J., Pappu R.V., Zhang F.*, Covalently-assembled, single-chain protein nanostructures with ultra-high stability. Nature Communications, 10, 3317. (2019)

Bowen C.H.*, Dai B.*, Sargent C.J., Bai W, Ladiwala P, Feng H., Huang W, Kaplan D.L., Galazka J.M., Zhang F., Recombinant Spidroins Replicate Mechanical Properties of Natural Spider Silk. Biomacromolecules, 19 (9), 3853–3860 (2018)

Jiang W., Qiao J.B., Bentley G.J., Liu D., Zhang F., Modular pathway engineering for the Production of Branched-Chain Fatty Alcohols. Biotechnol Biofuels. 10:244. (2017).

Xiao Y., Bowen C.H., Liu D., Zhang F., Exploiting non-genetic, cell-to-cell variation for enhanced biosynthesis. Nat Chem Biol 12, 339-344, (2016).

Bentley G.J., Jiang W., Xiao Y., Zhang F., Engineering Escherichia coli to Produce Branched-chain Fatty Acids in High Percentages. Metab Eng 38,148-158 (2016).

Zhang, F., Carothers, J.M., Keasling, J.D., Design of a dynamic sensor-regulator system for production of chemicals and fuels derived from fatty acids. Nat Biotechnol, 30, (4), 354-359 (2012)

Last Updated: 4/12/2022 2:51:08 PM

Microbial population control (cover issue of Nat Chem Biol)
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