The Sandarazols are Cryptic and Structurally Unique Plasmid-Encoded Toxins from a Rare Myxobacterium*.
Angew Chem Int Ed Engl
; 60(15): 8081-8088, 2021 04 06.
Article
em En
| MEDLINE
| ID: mdl-33534143
ABSTRACT
Herein, we describe a new plasmid found in Sandaracinusâ
sp. MSr10575 named pSa001 spanning 209.7â
kbp that harbors a cryptic secondary metabolite biosynthesis gene cluster (BGC). Activation of this BGC by homologous-recombination-mediated exchange of the native promoter sequence against a vanillate inducible system led to the production and subsequent isolation and structure elucidation of novel secondary metabolites, the sandarazolsâ
A-G. The sandarazols contain intriguing structural features and very reactive functional groups such as an α-chlorinated ketone, an epoxyketone, and a (2R)-2-amino-3-(N,N-dimethylamino)-propionic acid building block. In-depth investigation of the underlying biosynthetic machinery led to a concise biosynthetic model for the new compound family, including several uncommon biosynthetic steps. The chlorinated congener sandarazolâ
C shows an IC50 â
value of 0.5â
µm against HCTâ
116 cells and a MIC of 14â
µm against Mycobacterium smegmatis, which points at the sandarazols' potential function as defensive secondary metabolites or toxins.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Toxinas Biológicas
/
Myxococcales
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article