Global Awakening of Cryptic Biosynthetic Gene Clusters in Burkholderia thailandensis
| Autor: | Sudarshan Singh Thapa, Maheshi Dassanayake, Renesh Bedre, Anne Grove, Guannan Wang, Afsana Sabrin, Ashish Gupta |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Regulation of gene expression Genetics Burkholderia thailandensis Burkholderia 030106 microbiology Virulence Repressor General Medicine Gene Expression Regulation Bacterial Secondary metabolite Biology biology.organism_classification Biochemistry Biosynthetic Pathways 03 medical and health sciences Bacterial Proteins Multigene Family Gene expression medicine Molecular Medicine Gene Genome Bacterial medicine.drug |
| Zdroj: | ACS chemical biology. 12(12) |
| ISSN: | 1554-8937 |
| Popis: | Many bacteria encode biosynthetic proteins that produce a vast array of natural products. These compounds are often synthesized during host invasion as they function as virulence factors. In addition, such secondary metabolites have yielded numerous molecular scaffolds with pharmaceutical and clinical importance. The gene clusters that encode proteins responsible for synthesis of these compounds are typically silenced or "cryptic" under laboratory growth conditions, hampering discovery of novel lead compounds. We report here that MftR is a global repressor of secondary metabolite synthesis in Burkholderia thailandensis and that urate functions as a physiologically relevant inducer of gene expression. Biosynthetic gene clusters under MftR control include those associated with production of the antimicrobial bactobolins, the iron siderophore malleobactin, and the virulence factor malleilactone. MftR also controls additional genes associated with survival in a host environment, such as genes encoding components of the type III secretion system (T3SS) and proteins linked to anaerobic respiration. This observation not only has implications for understanding activation of gene regulatory networks during host invasion, but it also paves the way for isolation of novel therapeutic leads. |
| Databáze: | OpenAIRE |
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