Biofouling refers to the undesirable accumulation of microorganism, algae and animals on submerged substrates, resulting in tremendous economic losses to maritime industries around the world. A recent global ban on the use of organotins as antifouling agents has urgently demand for safe and effective antifouling agents developing from marine natural products. Accordingly, we have recently initiated a program to discover antifouling natural products from marine bacteria. Antifouling assessment of 49 isolates and their structure-activities relationship study revealed that furanone moieties were important functional groups in anti-larval settlement activity. Furthermore, two promising antifouling candidates, butenolides 3c-3d, were synthesized through structure optimization based on this SAR study. Additionally, to facilitate the discoveries of anti-bacteria (anti-microfouling) natural product, I established a de-replication approach for antibacterial screening. Taking advantage of LC-MS profiling and the anti-bacteria assay of bacterial crude extract, I rapidly identify a group of antibacterial candidates without isolation process, amicoumacins. However, the lack of genetic manipulation of the wide type producer strains hinders the biosynthesis studies of amicoumacins. To tackle this obstacle, I established a transformation-associated recombination (TAR)-based direct cloning, transfer and heterologous expression of natural products in B. subtilis and then succeeded in direct cloning and expression of a 47-kb nonribosomal peptide synthetase/polyketide synthase (NRPS/PKS) biosynthetic gene cluster for production of amicoumcins. My results clearly demonstrated that 1) Microbial natural products are potent but underexplored source of antifouling compounds; 2) Genus Bacillus are indeed a good source of compounds with interesting bioactive potential; 3) Direct cloning and heterologous expression of antibiotic natural products in the well-studied model organism Bacillus subtilis shall have a broad application in the study of natural products biosynthesis; 4) Chemical synthesis and biosynthesis of microbial natural products have been innovative solutions to the supply problem that inhibit the commercial development of antifouling marine natural products.
| Date of Award | 2014 |
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| Original language | English |
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| Awarding Institution | - The Hong Kong University of Science and Technology
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Biosynthesis and chemical synthesis study of antifouling marine natural products
Li, Y. (Author). 2014
Student thesis: Doctoral thesis