Research Progress in Area 4 方向 ( 四 ) 課題進展 195 Abstract Marine microbial-derived natural products are rarely discovered than terrestrials, usually with unique chemical structures and various bioactivities, which are considered promising drug-lead candidates. Prof. Qian’s team proposes to discover potential drug-lead compounds through the combination of genome mining techniques with their established in vitro & in vivo bioassays and field-study platforms. They plan to screen the bioactive compounds from the marine microorganisms’ secondary metabolites library and study their mode of action; to decipher the enigma of their biosynthesis pathways through activating biosynthesis gene clusters by WT mutation or heterologous expression. Research Activities and Progress • Discovered prenylated cyclopeptides, evaluated their neuroprotective activity, and elucidated the catalyticmechanismof P450 and their biosynthetic pathway; • Discovered antifouling activity of albofungins and evaluated its antifouling performance in marine environments; • Identified the chemical structure of bathiapeptides from a marine-derived Bacillus licheniformis and evaluated their anti-tumor activities; • Identified the chemical structure of griseocazines, evaluated their neuroprotective activity; • Revealed mode of action of elasnin against Methicillin-Resistant biofilm formation; • Discovered new chrexanthomycins of G4C2 G-quadruplex binding activity; • Identified biosynthetic pathway of chrexanthomycins with significant neuroprotective activity in Streptomyces chrestomyceticus; • Revealed TRPV1 inhibition activity of thiopeptide 1431. Key Findings • The crownlike cyclodipeptides of neuroprotective activities were discovered (Fig. 1); • A group of new antifouling compounds albofungins was discovered by targeting multiple fouling organisms; • A new family of compounds namely griseocazines were identified and presented potent neuroprotective activity; • A new family of compounds namely bathiapeptides were identified using a metabologenomics approach and showed strong cytotoxicity against tumor cell lines; • Elasnin inhibited biofilm formation; • Thiopeptide 1431 shows high selectivity on Methicillin-resistant Staphylococcus aureus, low cytotoxicity; it can significantly inhibit the activity of TRPV1; • Chrexanthomycins showed a high safety index, exclusively binding DNA and RNA G4C2 G-quadruplex; • Chrexanthomycins biosynthesis pathway was elucidated. Research Output Publication 8 Trained personnel 22 Evaluate the Biodiversity and Medicinal Potential of Marine Biofilm in the South China Sea Prof. Pei-Yuan Qian The Hong Kong University of Science and Technology Fig 1. Chemical structures of the identified compounds (1-5) and proposed mechanism of the CttpCmediated reactions. (Malit et al., 2021, Org. Lett.)
RkJQdWJsaXNoZXIy NDk5Njg=