My research focuses on Streptomyces biology, including microbial genetics, gene regulatory networks, and natural product discovery. I investigate the molecular mechanisms of regulatory systems, develop genetic engineering tools, and explore biosynthetic gene clusters to advance the discovery and production of novel bioactive compounds.

More information about Chaoxian Bai

Since brute force natural products (NPs) discovery does not yield the same result as it did in the past, we need to find a way to access the NPs lie hidden in the genomes of bacteria. Antibiotics are molecules that likely play a role in survival in a competitive environment, which has radically different from that in the laboratory. We therefore need to elucidate the triggers and cues that activate the expression of BGCs, and harness these to develop new drug-discovery approaches. Another way of exploiting the rich chemical diversity is to mine microbial genomes for promising BGCs and clone or even synthesize them followed by expression in heterologous production hosts. Since DNA from microbial communities in e.g. soil or sediments can be directly extracted and sequenced, this circumvents the problem that the vast majority of microbes cannot be cultivated in the laboratory.

During my MSc, I co-established a precise quantitative method based on flow cytometry and fluorescent protein at single-cell resolution in streptomycetes. We then developed and characterized hundreds of regulatory elements (e.g. promoters, Ribosome Binding Sites) by this method. These artificial regulatory elements were successfully applied in a proof-of-principle approach to activate and overproduce the cryptic lycopene gene cluster from Streptomyces avermitilis. Native BGCs are subject to complex regulation, which makes them often difficult to activate in the laboratory. Due to the interactions within the cellular and extracellular context, novel approaches are required for more predictable and reproducible expression of such BGCs. My PhD project has developed and deploy novel strategies to activate cryptic BGCs and identify their cognate NPs.

Key publications

• Inducible CRISPRi enables efficient and high-fidelity genome editing in Streptomyces. Chaoxian Bai, Hua Zhu, Lina M Bayona, Chao Du, Gilles P van Wezel. Nucleic Acids Research 54 11, 2026: https://doi.org/10.1093/nar/gkag560
• Construction and Diversification of Natural Product Biosynthetic Gene Clusters at High Efficiency and Accuracy. Chaoxian Bai. Lina M. Bayona, Gilles P. van Wezel. ACS Synth. Biol. 14 (11): 4574–4585, 2025: https://doi.org/10.1021/acssynbio.5c00601
• CUBIC: A Versatile Cumate-Based Inducible CRISPRi System in Streptomyces. Chaoxian Bai, Gilles P. van Wezel. ACS Synth. Biol. 12 (10): 3143–3147, 2023: https://doi.org/10.1021/acssynbio.3c00464

Publications