ArticleChembiochem : a European journal of chemical biology2014
Identification and characterization of the carbapenem MM 4550 and its gene cluster in Streptomyces argenteolus ATCC 11009.
Article in Chembiochem : a European journal of chemical biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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19 citing papers in PubMed, 27 citations in OpenAlex.
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- Biology and applications of co-produced, synergistic antimicrobials from environmental bacteria.Nature microbiology · 2021Review
- Identification and engineering of 32 membered antifungal macrolactone notonesomycins.Microbial cell factories · 2020Article
- Methylations in complex carbapenem biosynthesis are catalyzed by a single cobalamin-dependent radical S-adenosylmethionine enzyme.Chemical communications (Cambridge, England) · 2019Article
- Roles of 2-oxoglutarate oxygenases and isopenicillin N synthase in β-lactam biosynthesis.Natural product reports · 2018Review
- Sulfation and amidinohydrolysis in the biosynthesis of giant linear polyenes.Beilstein journal of organic chemistry · 2017Article
- Convergent biosynthetic pathways to β-lactam antibiotics.Current opinion in chemical biology · 2016Review
- Consecutive radical S-adenosylmethionine methylations form the ethyl side chain in thienamycin biosynthesis.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Intraspecies comparison of Streptomyces pratensis genomes reveals high levels of recombination and gene conservation between strains of disparate geographic origin.BMC genomics · 2014Article
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4 authors at 2 institutions in 1 country.
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Abstract
Nearly 50 naturally occurring carbapenem β-lactam antibiotics, most produced by Streptomyces, have been identified. The structural diversity of these compounds is limited to variance of the C-2 and C-6 side chains as well as the stereochemistry at C-5/C-6. These structural motifs are of interest both for their antibiotic effects and their biosynthesis. Although the thienamycin gene cluster is the only active gene cluster publically available in this group, more comparative information is needed to understand the genetic basis of these structural differences. We report here the identification of MM 4550, a member of the olivanic acids, as the major carbapenem produced by Streptomyces argenteolus ATCC 11009. Its gene cluster was also identified by degenerate PCR and targeted gene inactivation. Sequence analysis revealed that the genes encoding the biosynthesis of the bicyclic core and the C-6 and C-2 side chains are well conserved in the MM 4550 and thienamycin gene clusters. Three new genes, cmmSu, cmm17 and cmmPah were found in the new cluster, and their putative functions in the sulfonation and epimerization of MM 4550 are proposed. Gene inactivation showed that, in addition to cmmI, two new genes, cmm22 and -23, encode a two-component response system thought to regulate the production of MM 4550. Overexpression of cmmI, cmm22 and cmm23 promoted MM 4550 production in an engineered strain. Finally, the involvement and putative roles of all genes in the MM 4550 cluster are proposed based on the results of bioinformatics analysis, gene inactivation, and analysis of disruption mutants. Overall, the differences between the thienamycin and MM 4550 gene clusters are reflected in characteristic structural elements and provide new insights into the biosynthesis of the complex carbapenems.
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