Identification of trans-AT polyketide clusters in two marine bacteria reveals cryptic similarities between distinct symbiosis factors
| Autor: | Fernando de la Calle, Elena Gonzalez, Carmen Cuevas, Jörn Piel, Librada M. Cañedo, Carmen Schleissner, Dina Kačar, José Luis García, Pilar Rodríguez, Stefan Leopold-Messer, Beatriz Galán |
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| Přispěvatelé: | Ministerio de Economía y Competitividad (España), Kacar, Dina, Cañedo, Librada M., González, Elena G., Galán, Beatriz, Schleissner, Carmen, Leopold-Messer, Stefan, De la Calle, Fernando, García, José Luis, Kacar, Dina [0000-0002-0141-0357], Cañedo, Librada M. [0000-0002-1273-4138], González, Elena G. [0000-0002-4614-3889], Galán, Beatriz [0000-0002-2596-6034], Schleissner, Carmen [0000-0003-2979-7140], Leopold-Messer, Stefan [0000-0003-3490-3550], De la Calle, Fernando [0000-0001-8161-8299], García, José Luis [0000-0002-9238-2485] |
| Rok vydání: | 2020 |
| Předmět: |
Burkholderia gladioli
Trans-AT polyketide synthase Pederin Glutarimide-containing polyketides Microbiology Genome Streptomyces Natural product 03 medical and health sciences chemistry.chemical_compound Polyketide Gene cluster Rhodobacteraceae Symbiosis Sesbanimide Gene Ecology Evolution Behavior and Systematics 030304 developmental biology Whole genome sequencing Genetics 0303 health sciences Cytotoxic activity biology 030306 microbiology Alphaproteobacteria biology.organism_classification Orphan gene chemistry Multigene Family Polyketides Polyketide Synthases |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname |
| DOI: | 10.1101/2020.09.18.303172 |
| Popis: | 28 p.-5 fig.-1 tab. Glutarimide-containing polyketides are known as potent antitumoral and antimetastatic agents. The associated gene clusters have only been identified in a few Streptomyces producers and Burkholderia gladioli symbiont. The new glutarimide-family polyketides, denominated sesbanimides D, E and F along with the previously known sesbanimide A and C, were isolated from two marine alphaproteobacteria Stappia indica PHM037 and Labrenzia aggregata PHM038.Structures of the isolated compounds were elucidated based on 1D and 2D homo and heteronuclear NMR analyses and ESI-MS spectrometry. All compounds exhibited strong antitumor activity in lung, breast and colorectal cancer cell lines. Subsequent whole genome sequencing and genome mining revealed the presence of the trans-AT PKS gene cluster responsible for the sesbanimide biosynthesis, described as sbn cluster. Strikingly, the modular architecture of downstream mixed type PKS/NRPS, SbnQ, revealed high similarity to PedH in pederin and Lab13 in labrenzin gene clusters, although those clusters are responsible for the production of structurally completely different molecules. The unexpected presence of SbnQ homologs in unrelated polyketide gene clusters across phylogenetically distant bacteria, raises intriguing questions about the evolutionary relationship between glutarimide-like and pederin-like pathways, as well as the functionality of their synthetic products. The present study was funded by the Ministry of Economy and Competitiveness of Spain under the program RETOS-COLABORACIÓN with the project number RTC-2016-4892-1 (DESPOL). |
| Databáze: | OpenAIRE |
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