Solanimycin: Biosynthesis and Distribution of a New Antifungal Antibiotic Regulated by Two Quorum-Sensing Systems
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Solanimycin : Biosynthesis and Distribution of a New Antifungal Antibiotic Regulated by Two Quorum-Sensing Systems. / Matilla, Miguel A.; Monson, Rita E.; Murphy, Annabel; Schicketanz, Muriel; Rawlinson, Alison; Duncan, Caia; Mata, Juan; Leeper, Finian; Salmond, George P. C.
In: mBio, Vol. 13, No. 6, 2022.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Solanimycin
T2 - Biosynthesis and Distribution of a New Antifungal Antibiotic Regulated by Two Quorum-Sensing Systems
AU - Matilla, Miguel A.
AU - Monson, Rita E.
AU - Murphy, Annabel
AU - Schicketanz, Muriel
AU - Rawlinson, Alison
AU - Duncan, Caia
AU - Mata, Juan
AU - Leeper, Finian
AU - Salmond, George P. C.
PY - 2022
Y1 - 2022
N2 - The increasing emergence of drug-resistant fungal infections has necessitated a search for new compounds capable of combating fungal pathogens of plants, animals, and humans. Microorganisms represent the main source of antibiotics with applicability in agriculture and in the clinic, but many aspects of their metabolic potential remain to be explored. This report describes the discovery and characterization of a new antifungal compound, solanimycin, produced by a hybrid polyketide/nonribosomal peptide (PKS/NRPS) system in Dickeya solani, the enterobacterial pathogen of potato. Solanimycin was active against a broad range of plant-pathogenic fungi of global economic concern and the human pathogen Candida albicans. The genomic cluster responsible for solanimycin production was defined and analyzed to identify the corresponding biosynthetic proteins, which include four multimodular PKS/NRPS proteins and several tailoring enzymes. Antifungal production in D. solani was enhanced in response to experimental conditions found in infected potato tubers and high-density fungal cultures. Solanimycin biosynthesis was cell density dependent in D. solani and was controlled by both the ExpIR acyl-homoserine lactone and Vfm quorum-sensing systems of the bacterial phytopathogen. The expression of the solanimycin cluster was also regulated at the post-transcriptional level, with the regulator RsmA playing a major role. The solanimycin biosynthetic cluster was conserved across phylogenetically distant bacterial genera, and multiple pieces of evidence support that the corresponding gene clusters were acquired by horizontal gene transfer. Given its potent broad-range antifungal properties, this study suggests that solanimycin and related molecules may have potential utility for agricultural and clinical exploitation.
AB - The increasing emergence of drug-resistant fungal infections has necessitated a search for new compounds capable of combating fungal pathogens of plants, animals, and humans. Microorganisms represent the main source of antibiotics with applicability in agriculture and in the clinic, but many aspects of their metabolic potential remain to be explored. This report describes the discovery and characterization of a new antifungal compound, solanimycin, produced by a hybrid polyketide/nonribosomal peptide (PKS/NRPS) system in Dickeya solani, the enterobacterial pathogen of potato. Solanimycin was active against a broad range of plant-pathogenic fungi of global economic concern and the human pathogen Candida albicans. The genomic cluster responsible for solanimycin production was defined and analyzed to identify the corresponding biosynthetic proteins, which include four multimodular PKS/NRPS proteins and several tailoring enzymes. Antifungal production in D. solani was enhanced in response to experimental conditions found in infected potato tubers and high-density fungal cultures. Solanimycin biosynthesis was cell density dependent in D. solani and was controlled by both the ExpIR acyl-homoserine lactone and Vfm quorum-sensing systems of the bacterial phytopathogen. The expression of the solanimycin cluster was also regulated at the post-transcriptional level, with the regulator RsmA playing a major role. The solanimycin biosynthetic cluster was conserved across phylogenetically distant bacterial genera, and multiple pieces of evidence support that the corresponding gene clusters were acquired by horizontal gene transfer. Given its potent broad-range antifungal properties, this study suggests that solanimycin and related molecules may have potential utility for agricultural and clinical exploitation.
KW - Dickeya solani
KW - acyl-homoserine lactone
KW - agriculture and global food security
KW - antibiotics
KW - antifungal agents
KW - gene regulation
KW - horizontal gene transfer
KW - hybrid polyketide
KW - nonribosomal peptide
KW - phytopathogens
KW - post-transcriptional control mechanisms
KW - quorum sensing
KW - secondary metabolism
KW - DICKEYA-SOLANI
KW - NATURAL-PRODUCTS
KW - SALMONELLA-TYPHIMURIUM
KW - STRUCTURAL DIVERSITY
KW - ERWINIA-CAROTOVORA
KW - EMERGING FUNGAL
KW - SOFT-ROT
KW - VIRULENCE
KW - PLANT
KW - POTATO
U2 - 10.1128/mbio.02472-22
DO - 10.1128/mbio.02472-22
M3 - Journal article
C2 - 36214559
VL - 13
JO - mBio
JF - mBio
SN - 2161-2129
IS - 6
ER -
ID: 322872811