- Assistant Professor
- Chemical and Biological Engineering
- Engineering Research Center for Biorenewable Chemicals (CBiRC)
- Interdepartmental Microbiology Program
Main Office4140 Biorenewables Research Laboratory
Ames, IA 50011
Phone: 515 294-1132
Ph.D. Chemical Engineering, University of Illinois Urbana-Champaign, 2009
M.S. Chemical Engineering, University of Illinois Urbana-Champaign, 2005
B.S. Biochemistry and Molecular Biology, Nankai University, China, 2002
The advent of synthetic biology has revolutionized our ability to discover and construct new biosynthetic pathways and engineer platform organisms, or so-called microbial factories, to produce a wide variety of value-added products. Our laboratory focuses on engineering individual microorganisms as well as microbial consortia to address critical issues in energy sustainability and chemical production.
Engineering Non-Conventional Yeast
We are interested in exploring the potential of non-conventional yeast strains based on their special features that S. cerevisiae does not possess. For example, we study the transcriptomics and metabolomics of Pichia stipitis to understand its cellular metabolism regarding its high capacity of pentose utilization; we use the superior acid tolerance of Issatchenkia orientalis to create a superbug for producing short chain and medium chain fatty acids, the important precursors in industry for synthesizing polymers, surfactants, lubricants and biofuels.
Exploring Microbial Consortia
Microbial consortia, composed of multiple interacting microbial populations, can carry out complicated tasks that are more difficult or even impossible for individual populations to perform. The existence of such cooperation and division of labor are common in nature, where organisms establish mutual relationship. We can easily find such examples e.g. between bacteria for anaerobic methane oxidation, between plants and bacteria for global nitrogen fixation, and in higher animals where gut microbes facilitate food utilization and metabolite transfer. Here we exploit a genetically engineered microbial consortium of multiple yeast strains to address the issue of mixed sugar utilization in lignocellulosic hydrolysates.
Developing Strategies for High-Throughput Strain Optimization
We are interested in designing various protein, pathway and genome engineering strategies to systematically optimize strain performance. One example project is to develop a high-throughput sensing platform to report fatty acid product profiles. Fatty acid synthesis naturally occurs via six recurring reactions with two more carbons added in each cycle. Nowadays, production of fatty acids can easily be achieved through expressing the corresponding biosynthetic pathway in genetically trackable organisms. The challenge is how to produce a relatively pure fatty acid with a defined chain length. The product of natural fatty acid synthesis is usually a mixture of compounds with different chain lengths because the “gatekeeper” thioesterase (TE) hydrolyzes thioester bond promiscuously. In order to identify highly specific TEs to produce “pure” fatty acids, we engineer a series of transcriptional regulators responsive to fatty acids with defined chain lengths, as a high-throughput sensing platform, to report product profiles for the large library of TE variants.
- Z. Shao, J. Blodgett, B. Circello, A. Eliot, R. Woodyer, G. Li, A. van der Donk, W. M. Metcalf, and H. Zhao. “Biosynthesis of 2-Hydroxyethylphosphonate, an Unexpected Intermediate Common to Multiple Phosphonate Biosynthetic Pathways,” Journal of Biological Chemistry 283, 23161-8 (2008).
- Z. Shao, H. Zhao, and H. Zhao. “DNA Assembler, an in vivo Genetic Method for Rapid Construction of Large Recombinant DNA,” Nucleic Acids Research 37, e16 (2009).
- Z. Shao, Y. Luo, and H. Zhao. “Rapid Characterization and Engineering of Natural Product Biosynthetic Pathways via DNA Assembler,” Molecular Biosystems 7, 1056-9 (2011).
- J. Du, Z. Shao and H. Zhao. “Engineering Microbial Factories for Synthesis of Value-added Products,” Journal of Industrial Microbiology and Biotechnology 38, 873-90 (2011).
- J. Sun, Z. Shao, H. Zhao, N. Nair, F. Wen, J. Xu, and H. Zhao. “Systematic Characterization of a Panel of Constitutive Promoters for Applications in Pathway Engieering in Saccharomyces cerevisiae,” Biotechnology and Bioengineering 109(8), 2082-92 doi: 10.1002/bit.24481 (2012).
- Z. Shao and H. Zhao. “DNA Assembler: a Synthetic Biology Tool for Characterizing and Engineering Natural Product Gene Clusters,” Methods in Enzymology 517, 203-24 (2012).
- Z. Shao, G. Rao, C. Li, Z. Abil, Y. Luo, and H. Zhao. “Refactoring the Silent Spectinabilin Biosynthetic Pathway Using a Plug-and-Play Scaffold,” ACS Synthetic Biology 2(11), 662–9 doi:10.1021/sb400058n (2013, highlighted in front cover).
- Y. Luo,H. Huang, J. Liang, M. Wang, L. Lu, Z. Shao, R. E. Cobb, and H. Zhao. “Activation and Characterization of a Cryptic Polycyclic Tetramate Macrolactam Biosynthetic Gene Cluster,” Nature Communication Nature Communication 4, 2894 (2013).
- Z. Shao and H. Zhao. “Construction and Engineering of Large Biochemical Pathways via DNA Assembler,” Methods in Molecular Biology 1073, 85-106, doi: 10.1007/978-1-62703-625-2_9 (2013).