matsumotoense M-412 from the Avilés Canyon in the Cantabrian Sea
4. Conclusions
In summary, a new member of the paulomycin family that we have designated as paulomycin G has been obtained from cultures of Micromonospora matsumotoense M-412, isolated from deep-sea sediments collected at 2000 m depth in the submarine Avilés Canyon. Paulomycin G is a novel natural product, structurally unique since—to our knowledge—it is the first member of the paulomycin family of antibiotics lacking the paulomycose moiety, being the smallest bioactive paulomycin reported.
This new natural product displayed strong cytotoxic activity against human cancer cell lines such as pancreatic adenocarcinoma (MiaPaca_2), breast adenocarcinoma (MCF-7), and hepatocellular carcinoma (HepG2). Based on its cytotoxic activities, paulomycin G deserves to be considered as a candidate to perform further studies assessing its anticancer potential. Besides its unique structural features, paulomycin G might also be of interest in biosynthetic studies and useful for future paulomycin biosynthesis research or as a core structure in the generation of novel derivatives through combinatorial biosynthesis to generate structural diversity in the paulomycin family. Additionally, the isolation of a compound of the paulomycin family from a non-Streptomyces actinomycete is particularly noteworthy and suggests horizontal gene transfer between Micromonospora and Streptomyces species.
Supplementary Materials: The following are available online at www.mdpi.com/1660-3397/15/9/271/s1.
Figure S1: HPLC trace of the sample isolated; Figure S2: UV spectrum of compound 1; Figure S3: ESI-TOF spectra of compound 1; Figure S4: UV spectrum of compound 2; Figure S5: ESI-TOF spectra of compound 2;
Figure S6:1H NMR spectrum (DMSO-d6, 500 MHz) of compound 1; Figure S7:13C NMR spectrum (DMSO-d6, 125 MHz) of compound 1; Figure S8: COSY spectrum (DMSO-d6) of compound 1; Figure S9: HSQC spectrum (DMSO-d6) of compound 1; Figure S10: HMBC spectrum (DMSO-d6) of compound 1; Figure S11: ROESY spectrum (DMSO-d6) of compound 1; Figure S12: Picture of Micromonospora matsumotoense M-412.
Acknowledgments: This study was financially supported by Gobierno del Principado de Asturias (SV-PA-13-ECOEMP-62). The polarimeter, IR, and NMR equipment used in this work were acquired via grants for scientific and technological infrastructures from the Ministerio de Ciencia e Innovación (Grants Nos.
PCT-010000-2010-4 (NMR), INP-2011-0016-PCT-010000 ACT6 (polarimeter and IR)). The authors are grateful to all participants in the BIOCANT3 oceanographic expedition (DOSMARES) where Micromonospora matsumotoense M-412 was isolated. We are also grateful to J.A. Guijarro and J.L. Caso for continuous support. This is a contribution of the Asturias Marine Observatory.
Author Contributions: Aida Sarmiento-Vizcaíno isolated the strain and performed the phylogenetic analysis.
Alfredo F. Braña and Aida Sarmiento-Vizcaíno identified and performed the purification of the compound.
Ignacio Pérez-Victoria, Jesús Martín, and Fernando Reyes performed the structural elucidation of the compound.
Nuria de Pedro, Mercedes de la Cruz, Caridad Díaz and Francisca Vicente performed the biological tests.
José L. Acuña led the oceanographic expedition in which sediment samples were collected. Gloria Blanco and Fernando Reyes wrote the paper which was revised and approved by all the authors. Gloria Blanco and Luis A. García led and coordinated the research.
Conflicts of Interest: The authors declare no conflict of interest.
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