Recent application of metagenomic approaches toward the discovery of antimicrobials and other bioactive small molecules

Banik, Jacob J.; Brady, Sean F.

doi:10.1016/j.mib.2010.08.012

Cited by 119 publications

(99 citation statements)

References 47 publications

(35 reference statements)

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“…Traditional methods, involving exhaustive extractions of sponge, do not reveal the chemical diversity produced by these rare biosphere representatives, or pathways that are inactive within the native host (Chiang et al, 2010). Harnessing this potentially novel chemistry is, therefore, dependent on the ability of molecular approaches to identify where this diversity exists (Fieseler et al, 2007;Hochmuth et al, 2010;Trindade-Silva et al, 2012), to provide access to the genetic basis of biosynthesis (Piel et al, 2004a;Fisch et al, 2009;Banik and Brady, 2010;Brady et al, 2010) and ultimately to facilitate production of these molecules through heterologous expression within a suitable host (Fu et al, 2008;Craig et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Deep sequencing of non-ribosomal peptide synthetases and polyketide synthases from the microbiomes of Australian marine sponges

et al. 2013

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The biosynthesis of non-ribosomal peptide and polyketide natural products is facilitated by multimodular enzymes that contain domains responsible for the sequential condensation of amino and carboxylic subunits. These conserved domains provide molecular targets for the discovery of natural products from microbial metagenomes. This study demonstrates the application of tagencoded FLX amplicon pyrosequencing (TEFAP) targeting non-ribosomal peptide synthetase (NRPS) and polyketide synthase (PKS) genes as a method for determining the identity and diversity of natural product biosynthesis genes. To validate this approach, we assessed the diversity of NRPS and PKS genes within the microbiomes of six Australian marine sponge species using both TEFAP and metagenomic whole-genome shotgun sequencing approaches. The TEFAP approach identified 100 novel ketosynthase (KS) domain sequences and 400 novel condensation domain sequences within the microbiomes of the six sponges. The diversity of KS domains within the microbiome of a single sponge species Scopalina sp. exceeded that of any previously surveyed marine sponge. Furthermore, this study represented the first to target the condensation domain from NRPS biosynthesis and resulted in the identification of a novel condensation domain lineage. This study highlights the untapped potential of Australian marine sponges for the isolation of novel bioactive natural products. Furthermore, this study demonstrates that TEFAP approaches can be applied to functional genes, involved in natural product biosynthesis, as a tool to aid natural product discovery. It is envisaged that this approach will be used across multiple environments, offering an insight into the biological processes that influence the production of secondary metabolites.

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Section: Introductionmentioning

confidence: 99%

Deep sequencing of non-ribosomal peptide synthetases and polyketide synthases from the microbiomes of Australian marine sponges

et al. 2013

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“…Thus, the traditional culturing technique that is used to produce bioactive secondary metabolites from cultured microorganisms most likely missed the majority of bacterial-metabolites that exist in the nature (Banik & Brady, 2010).…”

Section: Another Emerging Approach In Ma-rine Drug Discoverymentioning

confidence: 99%

“…Metagenomics is basically a modern genomics approach to isolate the DNA of microbial communities directly from their natural environments (environmental DNA/eDNA), therefore difficulties associated with culturing the microbes can be avoided (Chen & Pachter, 2005). Since the genetic information that encoding the secondary metabolites produced by microorganism is typically clustered on the microorganisms' chromosomes, hence it is possible to predict the complete gene clusters of secondary metabolites biosynthesis on those organisms, which might provide a renewable source of the secondary metabolites (Banik & Brady, 2010). Once a gene has been identified, the genetic information can be used for compound production.…”

Section: Another Emerging Approach In Ma-rine Drug Discoverymentioning

confidence: 99%

An Emerging Marine Biotechnology: Marine Drug Discovery

Fajarningsih¹

2013

Squalen Bull. Marine Fisheries Postharvest Biotech.

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Marine natural resources offer an opportunity to discover a novel chemical diversity with interesting pharmacologically active compounds to treat many diseases such as cancer, inflammation, bacterial and parasitic infections, and many other diseases. Marine drug discovery is a rising area in marine biotechnology. Several hits of marine-derived drug compounds were approved; two of them are Ziconotide and Trabectedin. In 2004, Ziconotide was approved as pain treatment drugs in the United States and Europe. Then, in 2007, Trabectedin was also approved as anticancer drug in Europe. The main problem in marine drug discovery research is material supply problem. Up till now, strategies to overcome the problem are "Pharmaceutical aquaculture" of biologically active marine biota and chemical synthesis approach. Chemical synthesis approach is feasible solution to be used, especially when working with less complex structure of compounds. However, when working with structurally complex compounds where total or even semi synthesis was very difficult to be provided, aquaculture can be a solution. Currently, the use of microbiology, biochemistry, genetic, bioinformatics, genomic and meta-genomic has been intensifying in order to have a better result in marine natural product drug discovery. As chemical synthesis needs an expensive investment of advanced technology and highly skilled human resources, thus pharmaceutical aquaculture is more practicable to overcome the material supply insufficiency in Indonesia. Up till now, many Indonesian marine bioprospectors have been working with culturable marine microorganism to produce bioactive compounds and some others starting to work with genomic and metagenomic-based drug discovery.Keywords: Marine biotechnology, marine drug discovery, aquaculture, chemical synthesis ABSTRAK Kekayaan hayati laut menjadi sumber yang menjanjikan dalam kegiatan pencarian senyawa kimia baru dengan aktifitas farmakologi yang unggul sebagai kandidat obat kanker, peradangan, infeksi bakteri dan parasit, serta berbagai penyakit lainnya. Penemuan senyawa obat baru dari laut merupakan salah satu bidang penting dalam bioteknologi kelautan. Hingga saat ini, beberapa obat yang dikembangkan dari senyawa bahan alam laut telah disetujui penggunaannya; dua diantaranya adalah Ziconotide dan Trabectedin. Pada tahun 2004, Ziconotide telah disetujui penggunaannya sebagai obat pereda sakit di Amerika Serikat dan Eropa. Kemudian, pada tahun 2007, Trabectedin juga disetujui untuk digunakan sebagai obat antikanker di Eropa. Masalah utama dalam pengembangan senyawa obat dari laut adalah masalah pasokan bahan baku. Dua strategi yang saat ini digunakan untuk mengatasi masalah tersebut adalah dengan budidaya biota laut penghasil senyawa kimia aktif dan dengan pendekatan sintesis kimia. Ketika bekerja dengan struktur senyawa kimia yang tidak terlalu kompleks, pendekatan sintesis kimia dapat menjadi solusi untuk produksi senyawa kimia tersebut. Namun, ketika bekerja dengan senyawa kimia kompleks yang sulit untuk dilakukan ...

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“…Thereby, even the uncultivable microorganisms are addressed. The gathered genetic information is then scanned for potential biosynthetic genes in the hope for identification of novel natural products in a similar way as previously discussed (see section 4.5) (Banik & Brady, 2010;Miao & Davies, 2009). Alternatively, metagenomic expression libraries can also be directly assayed for functional products (Brady, 2007).…”

Section: Metagenomicsmentioning

confidence: 99%

“…Singh & Macdonald, 2010). Finally, it is imperative to enrich microbial populations for strains with potential to produce complex secondary metabolites (see section 4.2) (Miao & Davies, 2009) or enrich isolated eDNA samples for genes of interest (Banik & Brady, 2010) before the metagenomic library is constructed to minimize background.…”

Section: Metagenomicsmentioning

confidence: 99%