Activation of a silent phenazine biosynthetic gene cluster reveals a novel natural product and a new resistance mechanism against phenazines

Saleh, Orwah; Bonitz, Tobias; Flinspach, Katrin; Kulik, Andreas; Burkard, Nadja; Mühlenweg, Agnes; Vente, Andreas; Polnick, Stefan; Lämmerhofer, Michael; Gust, Bertolt; Fiedler, Hans‐Peter; Heide, Lutz

doi:10.1039/c2md20045g

Cited by 23 publications

(24 citation statements)

References 55 publications

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“…Whole genome sequencing has revealed that many soil microorganisms possess so-called cryptic gene clusters encoding for putative new secondary metabolites that are not produced during common in vitro conditions (Ikeda et al, 2003 ; Scherlach and Hertweck, 2009 ; Chiang et al, 2011 ; Saleh et al, 2012 ). In nature, however, antibiotics may be produced after perception of specific environmental signals (stress/nutrient signals) or signals from neighboring microorganisms (competitor sensing) (Firn and Jones, 2003 ; Cornforth and Foster, 2013 ; Zhu, 2014 ).…”

Section: Introductionmentioning

confidence: 99%

Impact of interspecific interactions on antimicrobial activity among soil bacteria

et al. 2014

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Certain bacterial species produce antimicrobial compounds only in the presence of a competing species. However, little is known on the frequency of interaction-mediated induction of antibiotic compound production in natural communities of soil bacteria. Here we developed a high-throughput method to screen for the production of antimicrobial activity by monocultures and pair-wise combinations of 146 phylogenetically different bacteria isolated from similar soil habitats. Growth responses of two human pathogenic model organisms, Escherichia coli WA321 and Staphylococcus aureus 533R4, were used to monitor antimicrobial activity. From all isolates, 33% showed antimicrobial activity only in monoculture and 42% showed activity only when tested in interactions. More bacterial isolates were active against S. aureus than against E. coli. The frequency of interaction-mediated induction of antimicrobial activity was 6% (154 interactions out of 2798) indicating that only a limited set of species combinations showed such activity. The screening revealed also interaction-mediated suppression of antimicrobial activity for 22% of all combinations tested. Whereas all patterns of antimicrobial activity (non-induced production, induced production and suppression) were seen for various bacterial classes, interaction-mediated induction of antimicrobial activity was more frequent for combinations of Flavobacteria and alpha- Proteobacteria. The results of our study give a first indication on the frequency of interference competitive interactions in natural soil bacterial communities which may forms a basis for selection of bacterial groups that are promising for the discovery of novel, cryptic antibiotics.

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Section: Introductionmentioning

confidence: 99%

Impact of interspecific interactions on antimicrobial activity among soil bacteria

et al. 2014

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“…CnqP2 –CnqP5 were found to group with the Mg 2+ -dependent prenyltransferases NphB from Streptomyces sp. CL190 and Ptf St from Streptomyces tendae [ 4 , 46 ]. Those are known to catalyse C - or O -prenylation of hydroxynaphthalenes as artificial aromatic substrates.…”

Section: Resultsmentioning

confidence: 99%

“…1,6-DHN is also known to be an artificial substrate of NphB [ 14 ] and other prenyltransferases [ 9 , 32 , 46 ]. Indeed, in our investigations CnqP2, CnqP3 and CnqP5 also accepted 1,6-DHN as the aromatic precursor.…”

Section: Resultsmentioning

confidence: 99%

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Diversity of ABBA Prenyltransferases in Marine Streptomyces sp. CNQ-509: Promiscuous Enzymes for the Biosynthesis of Mixed Terpenoid Compounds

et al. 2015

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Terpenoids are arguably the largest and most diverse family of natural products, featuring prominently in e.g. signalling, self-defence, UV-protection and electron transfer. Prenyltransferases are essential players in terpenoid and hybrid isoprenoid biosynthesis that install isoprene units on target molecules and thereby often modulate their bioactivity. In our search for new prenyltransferase biocatalysts we focused on the marine-derived Streptomyces sp. CNQ-509, a particularly rich source of meroterpenoid chemistry. Sequencing and analysis of the genome of Streptomyces sp. CNQ-509 revealed seven putative phenol/phenazine-specific ABBA prenyltransferases, and one putative indole-specific ABBA prenyltransferase. To elucidate the substrate specificity of the ABBA prenyltransferases and to learn about their role in secondary metabolism, CnqP1 –CnqP8 were produced in Escherichia coli and incubated with various aromatic and isoprenoid substrates. Five of the eight prenyltransferases displayed enzymatic activity. The efficient conversion of dihydroxynaphthalene derivatives by CnqP3 (encoded by AA958_24325) and the co-location of AA958_24325 with genes characteristic for the biosynthesis of THN (tetrahydroxynaphthalene)-derived natural products indicates that the enzyme is involved in the formation of debromomarinone or other naphthoquinone-derived meroterpenoids. Moreover, CnqP3 showed high flexibility towards a range of aromatic and isoprenoid substrates and thus represents an interesting new tool for biocatalytic applications.

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“…Whole genome sequencing has revealed that many soil microorganisms possess so-called cryptic gene clusters encoding for putative new secondary metabolites that are not produced during common in vitro conditions (Ikeda et al, 2003;Scherlach and Hertweck, 2009;Chiang et al, 2011;Saleh et al, 2012). In nature, however, antibiotics may be produced after perception of specific environmental signals (stress/nutrient signals) or signals from neighboring microorganisms (competitor sensing) (Firn, 2003;Cornforth and Foster, 2013;Zhu, 2014).…”

Section: Introductionmentioning

confidence: 99%

Mining into interspecific bacterial interactions

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Activation of a silent phenazine biosynthetic gene cluster reveals a novel natural product and a new resistance mechanism against phenazines

Cited by 23 publications

References 55 publications

Impact of interspecific interactions on antimicrobial activity among soil bacteria

Impact of interspecific interactions on antimicrobial activity among soil bacteria

Diversity of ABBA Prenyltransferases in Marine Streptomyces sp. CNQ-509: Promiscuous Enzymes for the Biosynthesis of Mixed Terpenoid Compounds

Mining into interspecific bacterial interactions

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