THESIS
2014
xvii leaves, 182 pages : illustrations (some color) ; 30 cm
Abstract
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 o...[
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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.
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