The Tripod for Bacterial Natural Product Discovery: Genome Mining, Silent Pathway Induction, and Mass Spectrometry-Based Molecular Networking

Trivella, Daniela Barretto Barbosa; Felício, Rafael de

doi:10.1128/msystems.00160-17

Cited by 39 publications

(31 citation statements)

References 15 publications

(26 reference statements)

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“…The discovery pipeline from these traditional sources has yielded little returns within recent times and the search for novel chemotherapeutics is now increasingly being focused on new techniques such as combinatorial chemistry, rational drug design, and genome mining. However, there is still potential for discovering novel antibiotic drug compounds from traditional natural product isolation and characterization [ 5 ]. This holds true especially for bacteria, whose genomes are considered plastic and variations even on the strain level can result in altered secondary metabolite profiles [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Isolation and Antibacterial Activity of Indole Alkaloids from Pseudomonas aeruginosa UWI-1

et al. 2020

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In this study, we report the first isolation of three antibiotic indole alkaloid compounds from a Pseudomonad bacterium, Pseudomonas aeruginosa UWI-1. The bacterium was batch fermented in a modified Luria Broth medium and compounds were solvent extracted and isolated by bioassay-guided fractionation. The three compounds were identified as (1) tris(1H-indol-3-yl) methylium, (2) bis(indol-3-yl) phenylmethane, and (3) indolo (2, 1b) quinazoline-6, 12 dione. A combination of 1D and 2D NMR, high-resolution mass spectrometry data and comparison from related data from the literature was used to determine the chemical structures of the compounds. Compounds 1–3 were evaluated in vitro for their antimicrobial activities against a wide range of microorganisms using the broth microdilution technique. Compounds 1 and 2 displayed antibacterial activity against only Gram-positive pathogens, although 1 had significantly lower minimum inhibitory concentration (MIC) values than 2. Compound 3 displayed potent broad-spectrum antimicrobial activity against a range of Gram positive and negative bacteria. Several genes identified from the genome of P. aeruginosa UWI-1 were postulated to contribute to the biosynthesis of these compounds and we attempted to outline a possible route for bacterial synthesis. This study demonstrated the extended metabolic capability of Pseudomonas aeruginosa in synthesizing new chemotypes of bioactive compounds.

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Section: Introductionmentioning

confidence: 99%

Isolation and Antibacterial Activity of Indole Alkaloids from Pseudomonas aeruginosa UWI-1

et al. 2020

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“…The term "genome mining" are associated to every bioinformatics investigation used to detect not only the biosynthetic pathway of bioactive natural products, but also their possible functional and chemical interactions [15]. Specifically, the genome mining involves the identification of previously uncharacterized natural product biosynthetic gene clusters within the genomes of sequenced organisms, sequence analysis of the enzymes encoded by these gene clusters, together with the experimental identification of the products of the gene clusters ( Figure 1; [16]). Genome mining is entirely dependent on computing technology and bioinformatics tools.…”

Section: Genome Miningmentioning

confidence: 99%

Genome Mining as New Challenge in Natural Products Discovery

et al. 2020

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Drug discovery is based on bioactivity screening of natural sources, traditionally represented by bacteria fungi and plants. Bioactive natural products and their secondary metabolites have represented the main source for new therapeutic agents, used as drug leads for new antibiotics and anticancer agents. After the discovery of the first biosynthetic genes in the last decades, the researchers had in their hands the tool to understand the biosynthetic logic and genetic basis leading to the production of these compounds. Furthermore, in the genomic era, in which the number of available genomes is increasing, genome mining joined to synthetic biology are offering a significant help in drug discovery. In the present review we discuss the importance of genome mining and synthetic biology approaches to identify new natural products, also underlining considering the possible advantages and disadvantages of this technique. Moreover, we debate the associated techniques that can be applied following to genome mining for validation of data. Finally, we review on the literature describing all novel natural drugs isolated from bacteria, fungi, and other living organisms, not only from the marine environment, by a genome-mining approach, focusing on the literature available in the last ten years.

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“…Since there is an increment in the number of whole-genome sequences of natural productsproducing microbes, the abundance of secondary metabolite producing biosynthetic gene clusters will also increase and be identified through the genome mining approach. It helps to identify clusters in genomic data to know about the corresponding chemical molecules, which is now widely used over the classical screening methods [50].…”

Section: Future Prospectsmentioning

confidence: 99%

Bioprocess and genetic engineering aspects of ascomycin production: a review

Sambyal

Singh

2020

Journal of Genetic Engineering and Biotechnology

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Background Ascomycin is a highly valuable multifunctional drug which exhibits numerous biological properties. Being an immunosuppressant, it is known to prevent graft rejection in humans and has potential to treat varying skin ailments. Its derivatives represent a novel class of anti-inflammatory macrolactams. But the biosynthetic machinery of ascomycin is still unclear. Main body of the abstract Due to the structural complexity, there occurs difficulty in its chemical synthesis; therefore, microbial production has been preferred by using Streptomyces hygroscopicus subsp. ascomyceticus. Through several genetic manipulation and mutagenesis techniques, the yield can be increased by several folds without any difficulties. Genetic engineering has played a significant role in understanding the biosynthetic pathway of ascomycin. Short conclusion Recently, many efforts have been made to utilize the therapeutic effects of ascomycin and its derivatives. This article covers concepts related to the production kinetics of ascomycin including an update of the ongoing yield improvement techniques as well as screening method of novel strains for ascomycin production.

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The Tripod for Bacterial Natural Product Discovery: Genome Mining, Silent Pathway Induction, and Mass Spectrometry-Based Molecular Networking

Cited by 39 publications

References 15 publications

Isolation and Antibacterial Activity of Indole Alkaloids from Pseudomonas aeruginosa UWI-1

Isolation and Antibacterial Activity of Indole Alkaloids from Pseudomonas aeruginosa UWI-1

Genome Mining as New Challenge in Natural Products Discovery

Bioprocess and genetic engineering aspects of ascomycin production: a review

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