Current strategies to induce secondary metabolites from microbial biosynthetic cryptic gene clusters

Begani, Jyotsna; Lakhani, Jyoti; Harwani, Dharmesh

doi:10.1007/s13213-018-1351-1

Cited by 24 publications

(22 citation statements)

References 157 publications

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“…Although the species of this industrially important genus are widely distributed, yet the rate of the discovery of novel natural products produced by them has been drastically reduced. Furthermore, an alarmingly high rate of the development of multidrug-resistance in microbial pathogens necessitates the search for yet undiscovered and metabolically potent actinomycete species from specialized niches such as deserts for potential new secondary metabolites [7][8][9]. In the present work, we report the draft genome sequence of Streptomyces sp.…”

Section: Streptomyces Have Linear Chromosomes and Their Genome Size Rmentioning

confidence: 99%

Comparative whole-genome analysis of a Thar desert strainStreptomycessp. JB150 provides deep insights into the encoded parvome and adaptations to desert edaphic system

Harwani

Begani

Lakhani

2021

Preprint

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We sequenced the genome of Streptomyces sp. JB150, isolated from a unique site of the Thar desert in India. Genome mining of the JB150 genome revealed the presence of many interesting secondary metabolic biosynthetic gene clusters (BGCs). The encoded parvome of JB150 includes non-ribosomal peptides, polyketides including β-lactone, butyrolactone, ectoine, lantipeptides, lasso peptides, melanin, resorcinol, siderophores, terpenoids, thiopeptides, and other types of hybrid compounds. Among them, ~30% BGCs displayed a high degree of novelty. The genome of JB150 was enriched for a large assortment of specialized genes coding for the production of many interesting biomolecules comprising compatible solutes, multiple stress-response regulators, transport proteins, protein secretion systems, signaling molecules, chaperones and storage reserves, etc. The presence of diverse members of CAZymes enzyme families, high numbers of riboflavin, flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), trehalose and aromatic compounds synthesis genes, putative orthologues to several of the classical fatty acid synthesis components, prototrophy for many essential amino acids exhibit metabolic versatility of JB150 to inhabit in the extreme desert environment. Besides, the genome of JB150 was observed to specifically encode thiazole-oxazole-modified thiazolemicrocin (TOMM) and ectoine. The comparison of the complete genomes of Streptomyces sp. JB150 and seven other actinomycete strains belonging to different desert ecosystems unveiled the presence of many previously undetected, distinctive, biological, and genomic signatures. We propose that these genetic traits endowed by these strains are essential for their adaptation in the highly underprivileged, extreme ecosystem of the Thar desert to cope with multiple abiotic stressors, oligotrophic nutrient conditions and to produce a huge repertoire of diverse secondary metabolites.

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Section: Streptomyces Have Linear Chromosomes and Their Genome Size Rmentioning

confidence: 99%

Comparative whole-genome analysis of a Thar desert strainStreptomycessp. JB150 provides deep insights into the encoded parvome and adaptations to desert edaphic system

Harwani

Begani

Lakhani

2021

Preprint

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“…In addition, the production of microbial compounds are frequently influenced by different cultivation parameters (e.g. nutrients, light, temperature, pH, and aeration) ( Bode et al 2002 , Pettit 2011 , Begani et al 2018 ) and identifying optimum growth conditions can require labour intensive screening. This has prompted the investigation of alternative approaches to identifying novel metabolites, such as high throughput screening (HTS) of synthetic compound libraries and fragment-based design ( Payne et al 2006 ; Doak et al 2016 ).…”

Section: Introductionmentioning

confidence: 99%

“…trimethoprim and piperacillin); ( Seyedsayamdost 2014 ), have also been shown to induce specialised metabolites in Burkholderia thailandensis . Systematic investigation into elicitors that awaken silent BGCs would have a major impact on drug discovery ( Begani et al 2018 ). Therefore, a rapid screening method to aid compound identification and obtain optimal producer strains, as well as allow the user to determine conditions needed to express these novel compounds, is urgently required to unlock the genetic potential of Burkholderia and other antibiotic producing microorganisms.…”

Section: Introductionmentioning

confidence: 99%

A rapid screening method for the detection of specialised metabolites from bacteria: Induction and suppression of metabolites from Burkholderia species

Webster

Mullins

et al. 2020

Journal of Microbiological Methods

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Screening microbial cultures for specialised metabolites is essential for the discovery of new biologically active compounds. A novel, cost-effective and rapid screening method is described for extracting specialised metabolites from bacteria grown on agar plates, coupled with HPLC for basic identification of known and potentially novel metabolites. The method allows the screening of culture collections to identify optimal production strains and metabolite induction conditions. The protocol was optimised on two Burkholderia species known to produce the antibiotics, enacyloxin IIa ( B. ambifaria ) and gladiolin ( B. gladioli ), respectively; it was then applied to strains of each species to identify high antibiotic producers. B. ambifaria AMMD and B. gladioli BCC0238 produced the highest concentrations of the respective antibiotic under the conditions tested. To induce expression of silent biosynthetic gene clusters, the addition of low concentrations of antibiotics to growth media was evaluated as known elicitors of Burkholderia specialised metabolites. Subinhibitory concentrations of trimethoprim and other clinically therapeutic antibiotics were evaluated and screened against a panel of B. gladioli and B. ambifaria . To enhance rapid strain screening with more antibiotic elicitors, antimicrobial susceptibility testing discs were included within the induction medium. Low concentrations of trimethoprim suppressed the production of specialised metabolites in B. gladioli , including the toxins, toxoflavin and bongkrekic acid. However, the addition of trimethoprim significantly improved enacylocin IIa concentrations in B. ambifaria AMMD. Rifampicin and ceftazidime significantly improved the yield of gladiolin and caryoynencin by B. gladioli BCC0238, respectively, and cepacin increased 2-fold with tobramycin in B. ambifaria BCC0191. Potentially novel metabolites were also induced by subinhibitory concentrations of tobramycin and chloramphenicol in B. ambifaria . In contrast to previous findings that low concentrations of antibiotic elicit Burkholderia metabolite production, we found they acted as both inducers or suppressors dependent on the metabolite and the strains producing them. In conclusion, the screening protocol enabled rapid characterization of Burkholderia metabolites, the identification of suitable producer strains, potentially novel natural products and an understanding of metabolite regulation in the presence of inducing or suppressing conditions.

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“…[1,4] Within microorganisms, actinobacteria represent the most promising group of bacteria that synthesize approximately two-thirds of all known natural bioactive products including some of the compounds most widely used as anticancer, anti-inflammatory, antibacterial, antifungal and antitumour agents etc. [5][6][7][8][9][10][11][12][13][14][15][16] Indeed, an estimated 70% or maybe more antibiotics currently used at the commercial levels are produced by the members of the genus Streptomyces in the phylum actinobacteria. .…”

Section: Introductionmentioning

confidence: 99%

Sand Dune Streptomyces JB66 Native to the Great Indian Thar Desert Inhibits Multidrug-Resistant Pathogens

Begani

Lakhani

Harwani

2019

Int. J. Pharm. Sci. Drug Res.

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The efficacy of an actinomycete strain JB66 recovered from a sand dune soil from the Bikaner district of the Thar desert in inhibiting the growth of various bacterial pathogens was studied. The type strains Staphylococcus aureus, Shigella flexneri, Klebsiella pneumoniae and the clinical isolates Escherichia coli, multidrug-resistant S. aureus and P. vulgaris were included in the antimicrobial assays. Polyphasic characterization of JB66 isolate revealed its identity as Streptomyces (MH762010). It showed 88.99-89.24% sequence similarity with the other members of this genus and share the maximum (88.89%) similarity with Streptomyces sp. ATSC13. The strain JB66 was found to produce a high amount of extracellular L-asparaginase, catalase, gelatinase, protease, tyrosinase and urease enzymes. The partial chemical categorization of the methanolic crude extract of the JB66 strain led to the preliminary identification of various metabolic compounds. The thin-layer chromatography fractionation revealed the presence of prodigiosin pigment or chandramycin, cephalosporin or zeatin, daidzein, demethoxy rapamycin, 4,6-dihydroxy-7-methoxyisoflavone, munumbicins and amiclenomycin like compounds. Bio-autography revealed that the metabolites localized at the Rf values of 0.40, 0.46 and 0.53 in TLC profile had the actual bioactive fractions. UV-VIS spectrum absorbance maxima at 288 nm revealed the presence of an aromatic nucleus.

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Current strategies to induce secondary metabolites from microbial biosynthetic cryptic gene clusters

Cited by 24 publications

References 157 publications

Comparative whole-genome analysis of a Thar desert strainStreptomycessp. JB150 provides deep insights into the encoded parvome and adaptations to desert edaphic system

Comparative whole-genome analysis of a Thar desert strainStreptomycessp. JB150 provides deep insights into the encoded parvome and adaptations to desert edaphic system

A rapid screening method for the detection of specialised metabolites from bacteria: Induction and suppression of metabolites from Burkholderia species

Sand Dune Streptomyces JB66 Native to the Great Indian Thar Desert Inhibits Multidrug-Resistant Pathogens

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