Genome mining and characterisation of multiple bioactive compounds from a Burkholderia gladioli isolate collection

Ca, Jones; Bull, MJ; Jenner, Matthew; Song, Lijiang; Dashti, Yousef; Harris, SR; Parkhill, Julian; Connor, TR; Challis, GL; Mahenthiralingam, Eshwar

doi:10.1055/s-0036-1596149

Cited by 3 publications

(2 citation statements)

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“…Systematic analyses of previously described natural products suggested the existence of large natural reservoirs of structural novelty still awaiting discovery (Gregory et al, 2019 ; Pye et al, 2017 ). This insight has been corroborated by genomic analyses of microbial producer strains, which have repeatedly documented the genetic potential for compound biosynthesis to vastly exceed the diversity of natural products detected in laboratory cultures (Aigle et al, 2014 ; Baltz, 2017 ; Jones et al, 2016 ). The majority of BGCs could not be matched to any detected product, and have thus frequently been interpreted as ‘silent’, that is not being expressed under standard laboratory conditions (Hoskisson & Seipke, 2020 ; Okada & Seyedsayamdost, 2017 ).…”

Section: Introductionmentioning

confidence: 90%

Bursts in biosynthetic gene cluster transcription are accompanied by surges of natural compound production in the myxobacterium Sorangium sp.

Boldt

Lukoseviciute

et al. 2023

Microbial Biotechnology

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A better understanding of the genetic regulation of the biosynthesis of microbial compounds could accelerate the discovery of new biologically active molecules and facilitate their production. To this end, we have investigated the time course of genome-wide transcription in the myxobacterium Sorangium sp. So ce836 in relation to its production of natural compounds. Time-resolved RNA sequencing revealed that core biosynthesis genes from 48 biosynthetic gene clusters (BGCs; 92% of all BGCs encoded in the genome) were actively transcribed at specific time points in a batch culture. The majority (80%) of polyketide synthase and non-ribosomal peptide synthetase genes displayed distinct peaks of transcription during exponential bacterial growth. Strikingly, these bursts in BGC transcriptional activity were associated with surges in the net production rates of known natural compounds, indicating that their biosynthesis was critically regulated at the transcriptional level. In contrast, BGC read counts from single time points had limited predictive value about biosynthetic activity, since transcription levels varied >100-fold among BGCs with detected natural products. Taken together, our time-course data provide unique insights into the dynamics of natural compound biosynthesis and its regulation in a wild-type myxobacterium, challenging the commonly cited notion of preferential BGC expression under nutrient-limited conditions. The close association observed between BGC transcription and compound production warrants additional efforts to develop genetic engineering tools for boosting compound yields from myxobacterial producer strains.

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Section: Introductionmentioning

confidence: 90%

Bursts in biosynthetic gene cluster transcription are accompanied by surges of natural compound production in the myxobacterium Sorangium sp.

Boldt

Lukoseviciute

et al. 2023

Microbial Biotechnology

View full text Add to dashboard Cite

show abstract

“…Systematic analyses of previously described natural products suggested the existence of large natural reservoirs of structural novelty still awaiting discovery (Gregory et al, 2019;Pye et al, 2017). This insight has been corroborated by genomic analyses of microbial producer strains, which have repeatedly documented the genetic potential for compound biosynthesis to vastly exceed the diversity of natural products detected in laboratory cultures (Aigle et al, 2014;Baltz, 2017;Jones et al, 2016). The majority of BGCs could not be matched to any detected product, and have thus frequently been interpreted as 'silent', i.e.…”

Section: Introductionmentioning

confidence: 94%

Bursts in biosynthetic gene cluster transcription are accompanied by surges of natural compound production in the myxobacteriumSorangiumsp

Boldt

Lukoseviciute

et al. 2022

Preprint

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We have investigated the time course of genome-wide transcription in the myxobacterium Sorangium sp. So ce836 in relation to its production of natural compounds. Time-resolved RNA sequencing revealed that core biosynthesis genes from 48 biosynthetic gene clusters (BGCs; 92% of all BGCs encoded in the genome) were actively transcribed at specific time points in a batch culture. The majority (80%) of polyketide synthase and non-ribosomal peptide synthetase genes displayed distinct peaks of transcription during exponential bacterial growth. Strikingly, these bursts in BGC transcriptional activity were associated with surges in the production of known natural compounds, indicating that their biosynthesis was critially regulated at the transcriptional level. In contrast, BGC read counts from single time points had limited predictive value about biosynthetic activity, since transcription levels varied >100-fold among BGCs with detected natural products. Taken together, our time-course data provide unique insights into the dynamics of natural compound biosynthesis and its regulation in a wild-type myxobacterium, challenging the commonly cited notion of preferential BGC expression under nutrient-limited conditions. The close association observed between BGC transcription and compound production warrants additional efforts to develop genetic engineering tools for myxobacterial producer strains, to boost compound yields by manipulating transcriptional activity.

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Genome mining for the search and discovery of bioactive compounds: The Streptomyces paradigm

Ward

Allenby²

2018

FEMS Microbiology Letters

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Genome mining and characterisation of multiple bioactive compounds from a Burkholderia gladioli isolate collection

Cited by 3 publications

References 0 publications

Bursts in biosynthetic gene cluster transcription are accompanied by surges of natural compound production in the myxobacterium Sorangium sp.

Bursts in biosynthetic gene cluster transcription are accompanied by surges of natural compound production in the myxobacterium Sorangium sp.

Bursts in biosynthetic gene cluster transcription are accompanied by surges of natural compound production in the myxobacteriumSorangiumsp

Genome mining for the search and discovery of bioactive compounds: The Streptomyces paradigm

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