RESUMEN
As part of a screening programme for antibiotic-producing bacteria, a novel Actinomadura species was discovered from a soil sample collected in Santorini, Greece. Preliminary 16S rRNA gene sequence comparisons highlighted Actinomadura macra as the most similar characterised species. However, whole-genome sequencing revealed an average nucleotide identity (ANI) value of 89% with A. macra, the highest among related species. Further phenotypic and chemotaxonomic analyses confirmed that the isolate represents a previously uncharacterised species in the genus Actinomadura, for which the name Actinomadura graeca sp. nov. is proposed (type strain 32-07T). The G+C content of A. graeca 32-07 is 72.36%. The cell wall contains DL-diaminopimelic acid, intracellular sugars are glucose, ribose and galactose, the predominant menaquinone is MK-9(H6), the major cellular lipid is phosphatidylinositol and fatty acids consist mainly of hexadecanoic acid. No mycolic acid was detected. Furthermore, A. graeca 32-07 has been confirmed as a novel producer of the non-ribosomal peptide antibiotic zelkovamycin and we report herein a provisional description of the unique biosynthetic gene cluster.
Asunto(s)
Actinomadura , Péptidos Catiónicos Antimicrobianos , Composición de Base , Compuestos Macrocíclicos/metabolismo , Actinomadura/clasificación , Actinomadura/genética , Actinomadura/metabolismo , Actinomadura/ultraestructura , Péptidos Catiónicos Antimicrobianos/biosíntesis , Péptidos Catiónicos Antimicrobianos/genéticaRESUMEN
Eight new angucyclic quinones, miaosporones A to H (1-8), along with the previously described metabolites 8-hydroxy-3-methylbenz[a]anthraquinone (9), tetrangulol (10), 5,6-dihydro-1,8-dihydroxy-3-methybenz[a]anthracene-7,12-quinone (11), and SF2315A (12), were isolated from the terrestrial actinomycete Actinomadura miaoliensis TBRC 5172 obtained from sediment collected from the Huai Yang reservoir, Prachuap Khiri Khan Province, Thailand. The relative and absolute configurations of the new compounds were determined from analysis of NMR spectroscopic and X-ray crystallographic data. Miaosporone A exhibited antimalarial activity against Plasmodium falciparum K1 and antibacterial activity against Mycobacterium tuberculosis with respective IC50 values of 2.5 and 2.4 µM and displayed cytotoxic activities against both cancerous (MCF-7 and NCI-H187) and nonmalignant (Vero) cells.
Asunto(s)
Actinomadura/metabolismo , Antiinfecciosos/aislamiento & purificación , Antineoplásicos/aislamiento & purificación , Quinolonas/aislamiento & purificación , Antiinfecciosos/farmacología , Antineoplásicos/farmacología , Línea Celular Tumoral , Humanos , Espectroscopía de Resonancia Magnética , Mycobacterium tuberculosis/efectos de los fármacos , Plasmodium falciparum/efectos de los fármacos , Quinolonas/química , Quinolonas/farmacologíaRESUMEN
Growth from spores activated a biosynthetic gene cluster in Actinomadura sp. RB29, resulting in the identification of two novel groups of halogenated polyketide natural products, named maduralactomycins and actinospirols. The unique tetracyclic and spirocyclic structures were assigned based on a combination of NMR analysis, chemoinformatic calculations, X-ray crystallography, and 13C labeling studies. On the basis of HRMS2 data, genome mining, and gene expression studies, we propose an underlying noncanonical angucycline biosynthesis and extensive post-polyketide synthase (PKS) oxidative modifications.