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Comprehensive Derivatization of Thioviridamides by Heterologous Expression
- Source :
- ACS chemical biology. 14(6)
- Publication Year :
- 2019
-
Abstract
- New technology for the derivatization of peptide natural products is required for drug development. Despite the recent advances in the genome sequencing technique enabling us to search for the biosynthetic genes for wide variety of natural products, the technical methods to get access to them are limited. A class of RiPPs, a recently emerged natural product family such as thioviridamide, is one of those possessing such unexplored chemical space. In this paper, we report a streamlined method to generate new thioviridamide derivatives and to assess their biological activities. Heterologous expression of 42 constructs in an engineered Streptomyces avermitilis host gave 35 designed thioviridamide derivatives, along with several unprecedented analogues. Moreover, cytotoxicity assay revealed that several derivatives showed more potent activities than those of prethioviridamide. These results indicate that this strategy can become one of the potential ways to produce supreme unnatural products.
- Subjects :
- 0301 basic medicine
Computational biology
Biology
01 natural sciences
Biochemistry
Peptides, Cyclic
DNA sequencing
03 medical and health sciences
chemistry.chemical_compound
Amino Acid Sequence
Derivatization
Biological Products
Natural product
010405 organic chemistry
General Medicine
biology.organism_classification
Chemical space
Streptomyces
0104 chemical sciences
Thioamides
030104 developmental biology
chemistry
Drug development
Molecular Medicine
Heterologous expression
Peptides
Streptomyces avermitilis
Biosynthetic genes
Subjects
Details
- ISSN :
- 15548937
- Volume :
- 14
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- ACS chemical biology
- Accession number :
- edsair.doi.dedup.....e3690e3ba2546d60b6c4b80dd8bf61ca