Education & Affiliations
Biography
Dr. Shuaihua Gao obtained a B.S. in Pharmaceutical Engineering from the Beijing University of Chemical and Technology where she did her undergraduate research with Prof. Guojun Zheng. During her undergraduate years, she studies the application of gamma-lactamase for the biosynthesis of anti-HIV drugs. After finishing her B.S., she started her PhD under the guidance of Prof. Guojun Zheng to focused on using microbial screening and genome mining methods to identify novel gamma-lactamases used for enantioselective reactions in preparation of anti-HIV drugs. In particular, she developed a high throughput colorimetric screening method for lactamase identification and protein engineering.
Dr. Gao joined Judith Klinman lab after finishing her PhD work within 3 years. In Klinman lab, she switched gears from translational science to basic science where she studied the fundamental and physical basis of enzyme catalysis. After obtaining her PhD, Dr. Gao returned to Klinman lab as a postdoc to continue studying the significance of protein dynamics in enzyme catalysis. She developed temperature dependent hydrogen deuterium exchange couple to mass spectrometry (TD-HDX-MS) to investigate the correlation between protein dynamics and enzyme efficiency.
Gao started her independent career in the Department of Chemical and Biomolecular Engineering at Tulane University in summer 2023. By integrating pharmaceutical chemistry, biochemistry, enzymology, protein engineering and bioinformatics, the Gao lab is tackling the problems in the world of both translational and basic science.
Research Interests
Protein engineering for biomedical applications. We perform protein engineering on a variety of naturally occurring proteins to enhance their catalytic performance via rapid cell-free protein synthesis and in vivo continuous directed evolution methodologies. One of the targeted proteins will be fluorinase that demonstrates application in radiotracer preparation for PET (positron emission tomography) scan to detect cancer cells.
Biosynthetic engineering for novel therapeutics. We focus on developing metabolic pathways to produce valuable molecules, engineering genetic systems to control pathways, and exploring fundamental questions in biochemistry and microbial biology. A case study will be rational design of non-ribosomal peptide synthetases (NRPS) microbial machineries to produce fluorinated novel NRPS products for antitumors, antibiotics, or immunosuppressants discovery.
Biophysical, molecular, and structural understanding of proteins relating to biological function. We apply biophysical probes including temperature dependent hydrogen deuterium exchange (HDX), NMR spectroscopy, and fluorescence spectroscopy to study the spatial and temporal resolution protein dynamics. This research emphasizes the importance of integrating dynamic factor for design of made-to-order proteins and promotes de novo design research progress.
Publications
Gao, S and Klinman, J. P., Functional roles of enzyme dynamics in accelerating active site chemistry: emerging techniques and changing concepts. Current Opinion in Structural Biology, 2022, 75, 102434. (Invited Review paper). https://www.sciencedirect.com/science/article/pii/S0959440X22001130?via%3Dihub
Gao, S.; Zhang, W.; Barrow, S. L.; Iavarone, A. T.; Klinman, J. P., Temperature-dependent hydrogen deuterium exchange shows impact of analog binding on adenosine deaminase flexibility but not embedded thermal networks. Journal of Biological Chemistry, 2022, 298(9), 102350. https://www.sciencedirect.com/science/article/pii/S0021925822007931?via%3Dihub
Gao, S.; Thompson, E. J.; Barrow, S. L.; Zhang, W.; Iavarone, A. T.; Klinman, J. P., Hydrogen–Deuterium Exchange within adenosine deaminase, a TIM barrel hydrolase, identifies networks for thermal activation of catalysis. Journal of the American Chemical Society 2020, 142 (47), 19936-19949. https://pubs.acs.org/doi/10.1021/jacs.1c01046
Zhang, J.; Balsbaugh, J. L.; Gao, S.; Ahn, N. G.; Klinman, J. P., Hydrogen deuterium exchange defines catalytically linked regions of protein flexibility in the catechol O-methyltransferase reaction. Proceedings of the National Academy of Sciences 2020, 117 (20), 10797-10805. https://www.pnas.org/doi/10.1073/pnas.1917219117?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed
Gao, S.; Lu, Y.; Li, Y.; Huang, R.; Zheng, G., Enhancement in the catalytic activity of Sulfolobus solfataricus P2 (+)-γ-lactamase by semi-rational design with the aid of a newly established high-throughput screening method. Applied microbiology and biotechnology 2019, 103 (1), 251-263. https://link.springer.com/article/10.1007/s00253-018-9428-0
Gao, S.; Zhu, S.; Huang, R.; Li, H.; Wang, H.; Zheng, G., Engineering the Enantioselectivity and Thermostability of a (+)-γ-Lactamase from Microbacterium hydrocarbonoxydans for Kinetic Resolution of Vince Lactam (2-Azabicyclo [2.2. 1] hept-5-en-3-one). Applied and environmental microbiology 2018, 84 (1). https://journals.asm.org/doi/10.1128/AEM.01780-17?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed
Gao, S.; Zhou, Y.; Zhang, W.; Wang, W.; Yu, Y.; Mu, Y.; Wang, H.; Gong, X.; Zheng, G.; Feng, Y., Structural insights into the γ-lactamase activity and substrate enantioselectivity of an isochorismatase-like hydrolase from Microbacterium hydrocarbonoxydans. Scientific reports 2017, 7, 44542. https://www.nature.com/articles/srep44542
Gao, S.; Huang, R.; Zhu, S.; Li, H.; Zheng, G., Identification and characterization of a novel (+)-γ-lactamase from Microbacterium hydrocarbonoxydans. Applied microbiology and biotechnology 2016, 100 (22), 9543-9553. https://link.springer.com/article/10.1007/s00253-016-7643-0
Gao, S.; Su, Y.; Zhao, L.; Li, G.; Zheng, G., Characterization of a (R)-selective amine transaminase from Fusarium oxysporum. Process Biochemistry 2017, 63, 130-136. https://www.sciencedirect.com/science/article/pii/S1359511317306712
Gao, S.; Zhu, S.; Huang, R.; Lu, Y.; Zheng, G., Efficient synthesis of the intermediate of abacavir and carbovir using a novel (+)-γ-lactamase as a catalyst. Bioorganic & Medicinal Chemistry Letters 2015, 25 (18), 3878-3881. https://www.sciencedirect.com/science/article/pii/S0960894X15007581
Chen, Y.; Gao, F.; Zheng, G.; Gao, S.,* Enantioselective synthesis of a chiral intermediate of himbacine analogs by Burkholderia cepacia lipase A. Biotechnology Letters 2020, 42 (12), 2643-2651. https://link.springer.com/article/10.1007/s10529-020-02969-z
Chen, Y.; Zhang, X.; Zheng, G.; Gao, S.,* Preparation of the enantiomerically enriched precursor of lamivudine (3TC™) via asymmetric catalysis mediated by Klebsiella oxytoca. Process Biochemistry 2019, 81, 77-84. https://www.sciencedirect.com/science/article/pii/S1359511319300790
Li, H.; Gao, S.; Qiu, Y.; Liang, C.; Zhu, S.; Zheng, G., Genome mining integrating semi-rational protein engineering and nanoreactor design: roadmap for a robust biocatalyst for industrial resolution of Vince lactam. Applied Microbiology and Biotechnology 2020, 104 (3), 1109-1123. https://link.springer.com/article/10.1007/s00253-019-10275-6
Shen, X.; Zhou, D.; Lin, Y.; Wang, J.; Gao, S.; Kandavelu, P.; Zhang, H.; Zhang, R.; Wang, B.-C.; Rose, J., Structural Insights into Catalytic Versatility of the Flavin-dependent Hydroxylase (HpaB) from Escherichia coli. Scientific reports 2019, 9 (1), 7087. https://www.nature.com/articles/s41598-019-43577-w
Su, Y.; Gao, S.; Li, H.; Zheng, G., Enantioselective resolution of γ-lactam utilizing a novel (+)-γ-lactamase from Bacillus thuringiensis. Process Biochemistry 2018, 72, 96-104. https://www.sciencedirect.com/science/article/pii/S1359511318305890
Zhu, S.; Huang, R.; Gao, S.; Li, X.; Zheng, G., Discovery and characterization of a second extremely thermostable (+)-γ-lactamase from Sulfolobus solfataricus P2. Journal of bioscience and bioengineering 2016, 121 (5), 484-490. https://www.sciencedirect.com/science/article/pii/S1389172315003710
Ren, L.; Zhu, S.; Shi, Y.; Gao, S.; Zheng, G., Enantioselective resolution of γ-lactam by a novel thermostable type II (+)-γ-lactamase from the hyperthermophilic archaeon Aeropyrum pernix. Applied biochemistry and biotechnology 2015, 176 (1), 170-184. https://link.springer.com/article/10.1007/s12010-015-1565-7
Zhu, S.; Gong, C.; Song, D.; Gao, S.; Zheng, G., Discovery of a novel (+)-γ-lactamase from Bradyrhizobium japonicum USDA 6 by rational genome mining. Applied and environmental microbiology 2012, 78 (20), 7492-7495. https://journals.asm.org/doi/full/10.1128/AEM.01398-12
