Biosynthesis Study Of Dalesindole Involved With AldoTL

Nature’s small molecules have played a prominent role in the history of organic chemistry. Over the past century, the complexity and diversity of natural product scaffolds and functional groups have been an inspiration to chemists’total synthesis, and they have also been an important source of drugs for the pharmaceutical industry. Nature’s small molecules to the genes that encode them has sparked a renaissance in natural product research, focusing primarily on the biosynthesis of polyketides and non-ribosomal peptides.In this thesis, the biosynthesis of dalesindole was studied.Chapter one reviewed the research biosynthesis progress of fungal alkaloids.The second chapter studied biosynthesis of dalesindole. By analysis the chemical structure of the new skeleton bioactive compound dalesindole, I realized the most important step of the whole biosynthesis pathway is the intermolecular aldol condensation reaction. Finally, I knockout the releated gene, and the mutant could not produce dalesindole from the I3C fed culture.The gene knockout platform of D.eschscholzii, and the biosynthesis of new skeleton poyketides and alkaloids. The knockout of KU70 gene and site-mutation of pyrG gene are the precondition of fungal gene knockout. In this study, I tried to knockout KU70 gene, and obtained a pyrG mutant strain.I established a highly effective method to knockout genes in D.eschscholzii. And I have extended the method to C.globosum and Curvularia sp. Then I tried to find out the gene behind the intermediate D by gene knockout, gene overexpression and gene heterologous expression.The last chapter sumerized this study.