Recently, the Team of Marine Molecular Ecology and Chemical Ecology from Guangzhou Marine Laboratory published a research paper titled “Genetic modifications boost chrexanthomycin yield and neuroprotective potential” in Journal of Advanced Research(a top-tier Q1 journal with an impact factor of 13). Prof. Pei-Yuan Qian and Prof. Aifang Cheng from the University of Macau (UM) served as co-corresponding authors of the paper, while Prof. Wei Ye (a visiting scholar of the team) and Dr. Wenkang Ye (a postdoctoral fellow) were the first authors. Guangzhou Marine Laboratory is the first-affiliated institution.The study achieved a new progress in genetic modification technology, successfully significantly increasing the yield of a class of rare natural products—chrexanthomycins. These compounds exhibit strong neural protective activities, opening up new avenues for the treatment of neurodegenerative diseases such as Alzheimer’s disease.
Neurodegenerative diseases are often accompanied by the gradual loss of neurons and have increasingly become a severe challenge threatening global population health. Natural products like chrexanthomycins show great potential and application prospects in neuroprotection; however, their extremely low natural yield has seriously hindered the progress of subsequent scientific research and clinical application. The joint research team of Guangzhou Marine Laboratory and the University of Macau aimed to overcome this bottleneck using genetic engineering technology.
The research team preliminarily deciphered the biosynthetic pathway through which Streptomyces chrestomyceticus synthesizes chrexanthomycins. By modifying key genes—specifically knocking out limiting factors and enhancing production promoters—the team successfully achieved an over ten-fold increase in the yield of the compound. Additionally, this genetic modification method also led to the successful obtainment of a new derivative: chrexanthomycin G. Laboratory tests showed that this derivative significantly improved memory ability in the Caenorhabditis elegans model and reduced the accumulation of β-amyloid protein (a marker of Alzheimer’s disease). The study highlights the potential of chrexanthomycin G as a therapeutic agent for the future treatment of Alzheimer’s disease and other neurodegenerative diseases. By enabling large-scale production of chrexanthomycins, this research has cleared a key barrier for its preclinical and clinical trials, bringing new hope for the treatment of neurodegenerative diseases that affect tens of millions of people worldwide.
This study was generously supported by the following funds: Guangdong Laboratory for Southern Marine Science and Engineering (Guangzhou); University Grants Committee (UGC) of the Government of the Hong Kong Special Administrative Region of China and its General Research Fund (GRF); National Natural Science Foundation of China; Science and Technology Development Fund of Macao - Scientific Research and Innovation Funding Scheme; and University of Macau Research Fund. The full paper is accessible at: https://doi.org/10.1016/j.jare.2025.08.064
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