Comparison of 10,11‐Dehydrocurvularin Polyketide Synthases from Alternaria cinerariae and Aspergillus terreus Highlights Key Structural Motifs |
| |
| Authors: | Rachel V K Cochrane Dr Zhizeng Gao Gareth R Lambkin Dr Wei Xu Prof Jaclyn M Winter Sandra L Marcus Prof Yi Tang Prof John C Vederas |
| |
| Affiliation: | 1. Department of Chemistry, University of Alberta, Edmonton, Alberta, Canada;2. Department of Chemical and Biomolecular Engineering and, Department of Chemistry and Biochemistry, University of California, Los Angeles, CA, USA;3. Department of Medicinal Chemistry, The University of Utah, Salt Lake City, Utah, USA |
| |
| Abstract: | Iterative type I polyketide synthases (PKSs) from fungi are multifunctional enzymes that use their active sites repeatedly in a highly ordered sequence to assemble complex natural products. A phytotoxic macrolide with anticancer properties, 10,11‐dehydrocurvularin (DHC), is produced by cooperation of a highly reducing (HR) iterative PKS and a non‐reducing (NR) iterative PKS. We have identified the DHC gene cluster in Alternaria cinerariae, heterologously expressed the active HR PKS (Dhc3) and NR PKS (Dhc5) in yeast, and compared them to corresponding proteins that make DHC in Aspergillus terreus. Phylogenetic analysis and homology modeling of these enzymes identified variable surfaces and conserved motifs that are implicated in product formation. |
| |
| Keywords: | bioinformatics biosynthesis dehydrocurvularin heterologous expression polyketide |
|
|
