<i>Burkholderia</i> as a Source of Natural Products

Kunakom, Sylvia; Eustáquio, Alessandra S.

doi:10.1021/acs.jnatprod.8b01068

Cited by 106 publications

(123 citation statements)

References 288 publications

(396 reference statements)

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“…Bacteria belonging to the Burkholderia genus are increasingly being recognised as an underexplored source of novel natural products. 52 Using a combination of carbon source modification and inactivation of the biosynthetic pathway for gladiolin, which is produced at high titre and interferes with the detection of lower abundance metabolites, we have identified gladiochelins A (1) and (2) as the metabolic product of a cryptic nonribosomal peptide biosynthetic gene cluster in B. gladioli. Similar approaches may prove useful for identifying the products of other cryptic Burkholderia biosynthetic gene clusters.…”

Section: Discussionmentioning

confidence: 99%

Discovery and biosynthesis of gladiochelins: unusual lipodepsipeptide siderophores fromBurkholderia gladioli

Dashti

Nakou

Mullins

et al. 2020

Preprint

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Burkholderia is a genus of diverse Gram-negative bacteria that includes several opportunistic pathogens. Siderophores, which transport iron from the environment into microbial cells, are important virulence factors in most pathogenic Burkholderia species. However, it is widely believed that Burkholderia gladioli, which can infect the lungs of cystic fibrosis (CF) sufferers, does not produce siderophores. B. gladioli BCC0238, isolated from the lung of a CF patient, produces two novel metabolites in a minimal medium containing glycerol and ribose as carbon sources. HPLC purification, followed by detailed spectroscopic analyses, identified these metabolites as unusual lipodepsipeptides containing a unique citrate-derived fatty acid and a rare dehydro-β-alanine residue. The absolute configurations of the amino acid residues in the two metabolites was elucidated using Marfey's method and the gene cluster responsible for their biosynthesis was identified by bioinformatics and insertional mutagenesis. In-frame deletions and enzyme activity assays were used to investigate the functions of several proteins encoded by the biosynthetic gene cluster, which was found in the genomes of most B. gladioli isolates, suggesting that its metabolic products play an important role in the growth and/or survival of the species. The Chrome Azurol S (CAS) assay showed the metabolites bind ferric iron and that this supresses their production when added to the growth medium. Moreover, a gene encoding a TonB-dependent ferric-siderophore receptor is adjacent to the biosynthetic genes. Together, these observations suggest that these metabolites likely function as siderophores in B. gladioli.

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Section: Discussionmentioning

confidence: 99%

Discovery and biosynthesis of gladiochelins: unusual lipodepsipeptide siderophores fromBurkholderia gladioli

Dashti

Nakou

Mullins

et al. 2020

Preprint

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“…Another important group of Gram-positive heterologous hosts is B. subtilis (Zhang et al, 2016). Burkholderia genomes contain up to 27 biosynthetic gene clusters, encoding compounds from diverse biosynthetic classes (Kunakom and Eustaquio, 2019). Moreover, Burkholderia has higher G + C DNA content (∼67%) than E. coli (∼50%).…”

Section: Heterologous Expression Of Lassomentioning

confidence: 99%

Lasso Peptides: Heterologous Production and Potential Medical Application

Cheng

Hua

2020

Front. Bioeng. Biotechnol.

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Lasso peptides are natural products found in bacteria. They belong to a specific family of ribosomally-synthesized and posttranslationally-modified peptides with an unusual lasso structure. Lasso peptides possess remarkable thermal and proteolytic stability and various biological activities, such as antimicrobial activity, enzyme inhibition, receptor blocking, anticancer properties and HIV antagonism. They have promising potential therapeutic effects on gastrointestinal diseases, tuberculosis, Alzheimer's disease, cardiovascular disease, fungal infections and cancer. Lasso peptides with high stability have been shown to be good carriers for other bioactive peptides. These make them attractive candidates for pharmaceutical research. This review aimed to describe the strategies used for the heterologous production of lasso peptides. Also, it indicated their therapeutical potential and their capacity to use as an efficient scaffold for epitope grafting.

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“…Burkholderia is a diverse genus of bacteria and a rich source of antimicrobial compounds ( 1 ). Modern natural product discovery is often guided by genome mining ( 2 ) and increasingly relies on large genome collections.…”

Section: Announcementmentioning

confidence: 99%