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Comparative analysis of a cryptic thienamycin-like gene cluster identified in Streptomyces flavogriseus by genome mining

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Abstract

In silico database searches allowed the identification in the S. flavogriseus ATCC 33331 genome of a carbapenem gene cluster highly related to the S. cattleya thienamycin one. This is the second cluster found for a complex highly substituted carbapenem. Comparative analysis revealed that both gene clusters display a high degree of synteny in gene organization and in protein conservation. Although the cluster appears to be silent under our laboratory conditions, the putative metabolic product was predicted from bioinformatics analyses using sequence comparison tools. These data, together with previous reports concerning epithienamycins production by S. flavogriseus strains, suggest that the cluster metabolic product might be a thienamycin-like carbapenem, possibly the epimeric epithienamycin. This finding might help in understanding the biosynthetic pathway to thienamycin and other highly substituted carbapenems. It also provides another example of genome mining in Streptomyces sequenced genomes as a powerful approach for novel antibiotic discovery.

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Acknowledgments

I thank the US Department of Energy Joint Genome Institute and the French National Genomic Institute of the CEA/Genoscope for making available genome-sequencing data prior to publication. This study was supported by a grant from the University of Oviedo (UNOV-10-MA-4). I want to thank Alfredo F. Braña for the fruitful discussions and critical reading of the manuscript and Luis A. García for his continuous support. I am very grateful to José L. Caso and José A. Guijarro for their valuable help.

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  1. Departamento de Biología Funcional e Instituto Universitario de Oncología del Principado de Asturias, Universidad de Oviedo, 33006, Oviedo, Spain

    Gloria Blanco

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  1. Gloria Blanco
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Correspondence to Gloria Blanco.

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Communicated by Jean-Luc Pernodet.

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Blanco, G. Comparative analysis of a cryptic thienamycin-like gene cluster identified in Streptomyces flavogriseus by genome mining. Arch Microbiol 194, 549–555 (2012). https://doi.org/10.1007/s00203-011-0781-y

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  • DOI: https://doi.org/10.1007/s00203-011-0781-y

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