Altered fatty acid composition in regulatory mutants of<i>Streptomyces cinnamonensis</i>

Pospı́šil, Stanislav; Řezanka, Tomáš; Víden, I.; Krumphanzl, V.; Ванек, З.

doi:10.1111/j.1574-6968.1985.tb01634.x

Cited by 4 publications

References 13 publications

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Biosynthesis of the Azoxy Compound Azodyrecin from Streptomyces mirabilis P8-A2

Maleckis,

Wibowo,

Gren

et al. 2024

ACS Chem. Biol.

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Azoxy compounds are a distinctive group of bioactive secondary metabolites characterized by a unique RN� N + (O − )R moiety. The azoxy moiety is present in various classes of metabolites that exhibit various biological activities. The enzymatic mechanisms underlying azoxy bond formation remain enigmatic. Azodyrecins are cytotoxic azoxy metabolites produced by Streptomyces mirabilis P8-A2. Here, we cloned and confirmed the putative azd biosynthetic gene cluster through CATCH cloning followed by expression and production of azodyrecins in two heterologous hosts, S. albidoflavus J1074 and S. coelicolor M1146, respectively. We explored the function of 14 enzymes in azodyrecin biosynthesis through gene knockout using CRISPR-Cas9 base editing in the native producer, S. mirabilis P8-A2. The key intermediates were analyzed in the mutants through MS/MS fragmentation studies, revealing azoxy bond formation via the conversion of hydrazine to an azo compound followed by further oxygenation. Enzymes involved in modifications of the precursor could be postulated based on their predicted function and the intermediates identified in the knockout strains. Moreover, the distribution of the azoxy biosynthetic gene clusters across Streptomyces spp. genomes is explored, highlighting the presence of these clusters in over 20% of the Streptomyces spp. genomes and revealing that azoxymycin and valanimycin are scarce, while azodyrecin and KA57A-like clusters are widely distributed across the phylogenetic tree.

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Biosynthesis of the Azoxy Compound Azodyrecin from Streptomyces mirabilis P8-A2

Maleckis,

Wibowo,

Gren

et al. 2024

ACS Chem. Biol.

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Biosynthesis of the azoxy compound azodyrecin fromStreptomyces mirabilisP8-A2

Maleckis,

Wibowo,

Gren

et al. 2023

Preprint

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Azoxy compounds are a distinctive group of bioactive secondary metabolites, characterized by a unique RN=N+(O-)R moiety. The azoxy moiety is present in various classes of metabolites that exhibit various biological activities. The enzymatic mechanisms underlying azoxy bond formation remain enigmatic. Azodyrecins are cytotoxic azoxy metabolites produced by Streptomyces mirabilis P8-A2. Here we cloned and confirmed the putative azd biosynthetic gene cluster through CATCH cloning followed by expression and production of azodyrecins in two heterologous hosts, S. albidoflavus J1074 and S. coelicolor M1146, respectively. We explored the function of 14 enzymes in azodyrecin biosynthesis through gene knock-out using CRISPR-Cas9 base editing in the native producer, S. mirabilis P8-A2. The key intermediates were analyzed in the mutants through MS/MS fragmentation studies, revealing azoxy bond formation via the conversion of hydrazine to azo compound; followed by further oxygenation. Additionally, N-oxygenase and dehydrogenase activities were confirmed among 8 core biosynthetic genes and five helper genes. Moreover, the distribution of the azoxy biosynthetic gene clusters across Streptomyces spp. genomes is explored, highlighting the presence of these clusters in over 20% of the Streptomyces spp. genomes and revealing that azoxymycin and valanimycin are scarce, while azodyrecin and KA57A like clusters are widely distributed across the phylogenetic tree.

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Nitrogen regulation of fatty acids and avermectins biosynthesis inStreptomyces avermitilis

Novák

Hájek

Řezanka

et al. 1992

FEMS Microbiology Letters

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Fatty acid composition was analysed in the producer of avermectins, Streptomyces avermitilis C‐18 grown in chemically defined medium with different nitrogen sources. Significant differences in nitrogen regulation of fatty acid biosynthesis were found in this strain in comparison with other streptomycetes studied so far. This finding could be explained at the level of regulation of branched‐chain amino acid metabolism.

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Altered fatty acid composition in regulatory mutants ofStreptomyces cinnamonensis

Cited by 4 publications

References 13 publications

Biosynthesis of the Azoxy Compound Azodyrecin from Streptomyces mirabilis P8-A2

Biosynthesis of the Azoxy Compound Azodyrecin from Streptomyces mirabilis P8-A2

Biosynthesis of the azoxy compound azodyrecin fromStreptomyces mirabilisP8-A2

Nitrogen regulation of fatty acids and avermectins biosynthesis inStreptomyces avermitilis

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