Academic Profile

Academic Profile

Prof Liang Zhao-Xun

Professor, School of Biological Sciences

Email: zxliang@ntu.edu.sg
Prof Liang Zhao-Xun

Biography
Education
Ph.D. degree in Chemistry, Northwestern University, USA (Supervised by Professor Brain Hoffman)
B.S. & M.S. degree in Organic Chemistry, Lanzhou University, Gansu, China

Employment
Sep 2005 - Present, Assistant, associate and full professor, School of Biological Sciences, Nanyang Technological University, Singapore
Jan 2002 - Jul 2005, Postdoc fellow, Department of Chemistry, University of California at Berkeley (with Professor Judith Klinman)
Research Interests
My research interests lie broadly at the interface of chemistry and biology. The main thrust of my research lab is to discover new proteins that underlie bacterial pathogenesis and novel enzymes in natural product biosynthesis. The two on-going research projects in our lab are:

Genomics-guided discovery of microbial enzymes and natural products - Soil and marine microorganisms produce a wide variety of secondary metabolites with spectacular chemical structure and potent biological activity. Relying on a genomics-guided approach, we focus on discovering microbial secondary metabolites produced by unusual biosynthetic pathways. After isolating phylogenetically unique soil and marine microbes from the tropic environment of South East Asia, we sequence and mine the genome of the microbes to identify novel biosynthetic pathways. We employ molecular biology and genome-editing tools to manipulate the biosynthetic gene clusters to gain access to targeted secondary metabolites. For microbes that are recalcitrant to genetic manipulation, we use synthetic biology tools to assemble the targeted biosynthetic gene clusters in heterologous hosts to produce the secondary metabolites. The function and mechanism of the novel biosynthetic enzymes that contribute to the biosynthesis of the secondary metabolites are further investigated by biochemical and structural studies. We expect the research work to yield novel bioactive natural products as well as biosynthetic enzymes that can be potentially exploited as biocatalysts.

Molecular mechanism underlying bacterial pathogenesis and antibiotic resistance - Cyclic dinucleotides that include c-di-GMP and c-di-AMP have emerged as prominent messengers in many multidrug-resistant pathogenic bacteria in recent years. Cyclic dinucleotides contribute to bacterial pathogenesis by mediating such important processes as virulence expression, antibiotic resistance, and biofilm formation. Accumulating evidence suggests that the cellular level of cyclic dinucleotides is controlled in a spatiotemporal manner by a complex network of enzymes and effector proteins. We are conducting biochemical, structural, and transcriptomic studies to understand cyclic dinucleotide-mediated mechanisms that underpin bacterial infection and antibiotic resistance. Given the vital role played by the cyclic nucleotides in both acute and chronic bacterial infection, the research will potentially unveil novel signaling proteins and pathways that can be targeted for developing antimicrobial and biofilm-controlling agents.

A full list of my publications can be found at https://scholar.google.com/citations?hl=en&user=F-DuOAkAAAAJ&view_op=list_works.Please contact me directly (zxliang@ntu.edu.sg) if you are interested in joining us.
Current Projects
  • A Novel Approach to Controlling Biofilm Thickness for Efficient Biocatalysis
  • A study of the biosynthetic mechanism of orchratoxin A for the control of toxin production in food commodities
  • Antimicrobial natural products from rare actinomycetes
  • Biosynthetic Mechanism of Antitumor Enediyne Natural Products
  • Design and Synthesis of Functional C-di-GMP Deriatives as Biological Probes and Antibacterial Agents
  • Discovery and engineering of nitrile oxidoreductase as biocatalysts for nitrile reduction
  • Function of c-di-GMP effectors in the human pathogen Pseudomonas aeruginosa
  • Heterologous production of cannabinoids in proprietary Streptomyces hosts
  • In situ cultivation of "unculturable" actinomycetes in micro-gel droplets
  • Structure and Function of the Polyketide Synthase in Enediyne Biosynthesis
  • Structure and function of novel antibiotic target fimX in apportunistic pathogen pseudomonas aeruginosa
  • Structure and regulation of c-di-GMP signalling proteins in pathogenic bacteria
  • Study of the Biosynthetic Mechanism of Salinosporamide A for Developing Novel Proteasome Inhibitors
Selected Publications
  • Ma GL, Chandra, H, Liang, Z.-X. (2020). Taming the flagellar motor of pseudomonads with a nucleotide messenger. Environmental Microbiology, 22, 2496–2513.
  • Z.J. Low, G-L. Ma, H. T. Tran, Y. Zou, X. Juan, L. Pang, S. Nuryyeva, Y. Hong, J. HuK, N. Houk, Z.-X. Liang. (2020). Sungeidines from a Non-canonical Enediyne Biosynthetic Pathway. Journal of the American Chemical Society, 142(4), 1673-1679.
  • Linghui Xu, Lingyi Xin, Yukai Zeng, Joey Kuok Hoong Yam, Yichen Ding, Prabhadevi Venkataramani, Qing Wei Cheang, Xiaobei Yang, Xuhua Tang, Lian-Hui Zhang, Keng-Hwee Chiam, Liang Yang, Zhao-Xun Liang. (2016). A cyclic di-GMP–binding adaptor protein interacts with a chemotaxis methyltransferase to control flagellar motor switching. Science Signaling, 9, ra102.
  • Ho, C. L., Chong, K. S. J., Oppong, J. A., Chuah, M. L. C., Tan, S. M., *Liang, Z.-X. (2013). Visualizing the perturbation of cellular cyclic di-GMP levels in bacterial cells.. Journal of the American Chemical Society, 135, 566-569.
  • Sun H, Ho CL, Ding F, Soehano I, Liu X-W, and Liang Z-X. (2012). Synthesis of (R)-Mellein by a Partially Reducing Iterative Polyketide Synthase. Journal of the American Chemical Society, 134(29), 11924–11927.

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