Journal
TETRAHEDRON LETTERS
Volume 54, Issue 23, Pages 2999-3002Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.tetlet.2013.03.120
Keywords
Cytochalasin; Biosynthesis; Polyketide synthase; Non-ribosomal peptide synthetase; Fungal metabolite
Categories
Funding
- Japan Society for the Promotion of Science (JSPS) [22108002]
- JSPS
- Grants-in-Aid for Scientific Research [22108007] Funding Source: KAKEN
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Cytochalasins are an important class of fungal natural products in view of structural diversity and biological activities. Although their biosynthetic studies have been examined extensively, the detailed molecular assembly mechanism remains to be solved. We have succeeded to heterologously express the cytochalasin polyketide synthase-non-ribosomal peptide synthetase (PKS-NRPS) hybrid gene ccsA and the trans-acting enoyl-CoA reductase gene ccsC in Aspergillus oryzae. The resultant transformant produced a novel metabolite possessing the cytochalasin backbone. This established that CcsA is capable of constructing the octaketide connected with phenylalanine in collaboration with CcsC, and that CcsA R domain catalyzes reductive cleavage of the thio-tethered PKS-NRPS product. (C) 2013 Elsevier Ltd. All rights reserved.
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