The erythromycin biosynthetic gene cluster of Aeromicrobium erythreum

Brikun, Igor A.; Reeves, Andrew R.; Cernota, William H.; Luu, Minh B.; Weber, Jesse N.

doi:10.1007/s10295-004-0154-5

Cited by 23 publications

(12 citation statements)

References 45 publications

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“…Both species have biosynthetic gene clusters extremely similar to the ery cluster in S. erythraea but contain putative regulatory genes. In A. erythreum, a transcriptional regulator of the MarR family (ery-ORF25) is encoded at one end of the ery cluster adjacent to eryCI (16), and in M. megalomicea, a putative regulator is encoded at the end adjacent to megDVI (17).…”

Section: Resultsmentioning

confidence: 99%

A key developmental regulator controls the synthesis of the antibiotic erythromycin in Saccharopolyspora erythraea

Chng

Lum

Vroom

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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Saccharopolyspora erythraea makes erythromycin, an antibiotic commonly used in human medicine. Unusually, the erythromycin biosynthetic (ery) cluster lacks a pathway-specific regulatory gene. We isolated a transcriptional regulator of the ery biosynthetic genes from S. erythraea and found that this protein appears to directly link morphological changes caused by impending starvation to the synthesis of a molecule that kills other bacteria, i.e., erythromycin. DNA binding assays, liquid and affinity chromatography, MALDI-MS analysis, and de novo sequencing identified this protein (M r ‫؍‬ 18 kDa) as the S. erythraea ortholog of BldD, a key regulator of development in Streptomyces coelicolor. Recombinant S. erythraea BldD bound to all five regions containing promoters in the ery cluster as well as to its own promoter, the latter with an order-of-magnitude stronger than to the ery promoters. Deletion of bldD in S. erythraea decreased the erythromycin titer in a liquid culture 7-fold and blocked differentiation on a solid medium. Moreover, an industrial strain of S. erythraea with a higher titer of erythromycin expressed more BldD than a wild-type strain during erythromycin synthesis. Together, these results suggest that BldD concurrently regulates the synthesis of erythromycin and morphological differentiation. The ery genes are the first direct targets of a BldD ortholog to be identified that are positively regulated.cell differentiation ͉ secondary metabolites ͉ BldD

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Section: Resultsmentioning

confidence: 99%

A key developmental regulator controls the synthesis of the antibiotic erythromycin in Saccharopolyspora erythraea

Chng

Lum

Vroom

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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“…To address this possibility, experiments were performed using two different erythromycin-producing organisms, S. erythraea and Aeromicrobium erythreum (2), in order to test for ␤-glucosidase activity against isoflavone glucosides. The hypothesis was that if the eryBI gene was found to be involved in the conversion of isoflavone glucosides, then inactivation of eryBI could make the recovery of isoflavone glucoside coproducts from erythromycin fermentation possible without interfering with erythromycin production.…”

mentioning

confidence: 99%

Knockout of the Erythromycin Biosynthetic Cluster Gene, eryBI , Blocks Isoflavone Glucoside Bioconversion during Erythromycin Fermentations in Aeromicrobium erythreum but Not in Saccharopolyspora erythraea

Reeves

Seshadri

Brikun

et al. 2008

Appl Environ Microbiol

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Isoflavone glucosides are valuable nutraceutical compounds and are present in commercial fermentations, such as the erythromycin fermentation, as constituents of the soy flour in the growth medium. The purpose of this study was to develop a method for recovery of the isoflavone glucosides as value-added coproducts at the end of either Saccharopolyspora erythraea or Aeromicrobium erythreum fermentation. Because the first step in isoflavone metabolism was known to be the conversion of isoflavone glucosides to aglycones by a ␤-glucosidase, we chose to knock out the only ␤-glucosidase gene known at the start of the study, eryBI, to see what effect this had on metabolism of isoflavone glucosides in each organism. In the unicellular erythromycin producer A. erythreum, knockout of eryBI was sufficient to block the conversion of isoflavone glucosides to aglycones. In S. erythraea, knockout of eryBI had no effect on this reaction, suggesting that other ␤-glucosidases are present. Erythromycin production was not significantly affected in either strain as a result of the eryBI knockout. This study showed that isoflavone metabolism could be blocked in A. erythreum by eryBI knockout but that eryBI knockout was not sufficient to block isoflavone metabolism in S. erythraea.

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“…Multiple clusters can be associated with a given compound family. For example, epothilone biosynthetic gene clusters have been sequenced from two strains of Sorangium cellulosum (20,21), and erythromycin gene clusters have been sequenced from Saccharopolyspora erythraea (22) and Aeromicrobium erythreum (11). Each cluster is associated with an NCBI nucleotide record.…”

Section: Database Organizationmentioning

confidence: 99%

“…For example, they may lack a characterized product as is seen for a large number of cryptic or silent gene clusters from whole genome sequencing efforts (10). The result of this is a bias towards a limited number of well-known archetypical clusters, such as the erythromycin (accession number AY623658) (11) and tyrocidine (accession number AF004835) (12) gene clusters. This is a particularly important concern for researchers attempting to assign function to new gene clusters and those involved in bioprospecting, as they need access to the breath and diversity of sequenced clusters and not simply the well-known prototypical textbook clusters.…”

Section: Introductionmentioning

confidence: 99%

ClusterMine360: a database of microbial PKS/NRPS biosynthesis

Conway

Boddy

2012

Nucleic Acids Research

115

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ClusterMine360 (http://www.clustermine360.ca/) is a database of microbial polyketide and non-ribosomal peptide gene clusters. It takes advantage of crowd-sourcing by allowing members of the community to make contributions while automation is used to help achieve high data consistency and quality. The database currently has >200 gene clusters from >185 compound families. It also features a unique sequence repository containing >10 000 polyketide synthase/non-ribosomal peptide synthetase domains. The sequences are filterable and downloadable as individual or multiple sequence FASTA files. We are confident that this database will be a useful resource for members of the polyketide synthases/non-ribosomal peptide synthetases research community, enabling them to keep up with the growing number of sequenced gene clusters and rapidly mine these clusters for functional information.

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The erythromycin biosynthetic gene cluster of Aeromicrobium erythreum

Cited by 23 publications

References 45 publications

A key developmental regulator controls the synthesis of the antibiotic erythromycin in Saccharopolyspora erythraea

A key developmental regulator controls the synthesis of the antibiotic erythromycin in Saccharopolyspora erythraea

Knockout of the Erythromycin Biosynthetic Cluster Gene, eryBI , Blocks Isoflavone Glucoside Bioconversion during Erythromycin Fermentations in Aeromicrobium erythreum but Not in Saccharopolyspora erythraea

ClusterMine360: a database of microbial PKS/NRPS biosynthesis

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