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GNPS - Dataset Creation from GNPS Molcular Networking - e160b564fc7e48e6b82394991bfd79be

ABSTRACT: Metabolic profiles of Actinobacteria isolated from a faecal sample that was taken from the intestinal tracts of a 28,000-year-old Siberian Mammoth. Strains have been grown on Nutrient Agar (Difco) for one week before metabolite extraction with ethyl acetate. 720-722: medium blank 723-725: Oerskovia sp. M15 726-728: Streptomyces sp. M19 729-731: Saccharopolyspora sp. M46 732-734: Streptomyces sp. M10

INSTRUMENT(S): Shimadzu 9030 QTOF mass spectrometer

ORGANISM(S): Sanguibacter (ncbitaxon:60919) Saccharopolyspora (ncbitaxon:1835) Micromonospora (ncbitaxon:1873) Streptomyces (ncbitaxon:1883) Oerskovia (ncbitaxon:162491)

SUBMITTER: Gilles van Wezel

PROVIDER: MSV000093121 | GNPS | Mon Oct 16 07:22:00 BST 2023

REPOSITORIES: GNPS

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Project description:Actinobacteria provide a rich spectrum of bioactive natural products and therefore display an invaluable source towards commercially valuable pharmaceuticals and agrochemicals. Here, we studied the use of inorganic talc microparticles (hydrous magnesium silicate, 3MgO·4SiO2·H2O, 10 µm) as a general supplement to enhance natural product formation in this important class of bacteria. Added to cultures of recombinant Streptomyces lividans, talc (10 g L-1) enhanced production of the macrocyclic peptide antibiotic bottromycin A2 and its methylated derivative Met-bottromycin A2 up to 43%. Hereby, the microparticles fundamentally affected metabolism. With talc, S. lividans grew to 40% smaller pellets and, using RNA sequencing, revealed accelerated morphogenesis and aging, indicated by early upregulation of developmental regulator genes such as ssgA, ssgB, wblA, sigN and bldN. Furthermore, the microparticles re-balanced the expression of individual bottromycin cluster genes, resulting in a higher macrocyclization efficiency at the level of BotAH and correspondingly lower levels of non-cyclized shunt by-products, driving the production of mature bottromycin. Testing a variety of Streptomyces species, talc addition resulted in up to 13-fold higher titers for the RiPPs bottromycin and cinnamycin, the alkaloid undecylprodigiosin, the polyketide pamamycin, the tetracycline-type oxytetracycline, and the anthramycin-analogues usabamycins. Moreover, talc addition boosted production in other actinobacteria, outside of the genus of Streptomyces: vancomycin (Amycolatopsis japonicum DSM 44213), teicoplanin (Actinoplanes teichomyceticus ATCC 31121), and the angucyclinone-type antibiotic simocyclinone (Kitasatospora sp. DSM 102431). For teicoplanin, the microparticles were even crucial to activate production. Taken together, the use of talc was beneficial in 75% of all tested cases and optimized natural and heterologous hosts forming the substance of interest with clusters under native and synthetic control. Given its simplicity and broad benefits, microparticle-supplementation appears as an enabling technology in natural product research of these most important microbes.

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GNPS - Dataset Creation from GNPS Molcular Networking - e160b564fc7e48e6b82394991bfd79be

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