Mini review: Genome mining approaches for the identification of secondary metabolite biosynthetic gene clusters in Streptomyces

Lee, Namil; Hwang, Soonkyu; Kim, Jihun; Cho, Suhyung; Palsson, Bernhard Ø.; Cho, Byung-Kwan

doi:10.1016/j.csbj.2020.06.024

Cited by 129 publications

(124 citation statements)

References 104 publications

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“…Moreover, ongoing advances in gene mining, comparative transcriptomics, metabolomics, and other bioinformatic tools have made them promising methods for discovering natural products from actinomycetes ( Boddy, 2014 ). By combining genome mining approaches with antiSMASH tools, bacterial PKs and non-ribosomal peptides (NRPs), as well as complex secondary metabolites with antimicrobial, antiviral, anti-infective, or anticancer properties, have been identified ( Lee et al, 2020a ). These new characterization methods have also predicted new biosynthetic pathways and their related natural compounds.…”

Section: Introductionmentioning

confidence: 99%

Multi-omics Comparative Analysis of Streptomyces Mutants Obtained by Iterative Atmosphere and Room-Temperature Plasma Mutagenesis

et al. 2021

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Sponges, the most primitive multicellular animals, contain a large number of unique microbial communities. Sponge-associated microorganisms, particularly actinomyces, have the potential to produce diverse active natural products. However, a large number of silent secondary metabolic gene clusters have failed to be revived under laboratory culture conditions. In this study, iterative atmospheric room-temperature plasma. (ARTP) mutagenesis coupled with multi-omics conjoint analysis was adopted to activate the inactive wild Streptomyces strain. The desirable exposure time employed in this study was 75 s to obtain the appropriate lethality rate (94%) and mutation positive rate (40.94%). After three iterations of ARTP mutagenesis, the proportion of mutants exhibiting antibacterial activities significantly increased by 75%. Transcriptome analysis further demonstrated that the differential gene expression levels of encoding type I lasso peptide aborycin had a significant upward trend in active mutants compared with wild-type strains, which was confirmed by LC-MS results with a relative molecular mass of 1082.43 ([M + 2H]2+ at m/z = 2164.86). Moreover, metabolome comparative analysis of the mutant and wild-type strains showed that four spectra or mass peaks presented obvious differences in terms of the total ion count or extracting ion current profiles with each peak corresponding to a specific compound exhibiting moderate antibacterial activity against Gram-positive indicators. Taken together, our data suggest that the ARTP treatment method coupled with multi-omics profiling analysis could be used to estimate the valid active molecules of metabolites from microbial crudes without requiring a time-consuming isolation process.

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Section: Introductionmentioning

confidence: 99%

Multi-omics Comparative Analysis of Streptomyces Mutants Obtained by Iterative Atmosphere and Room-Temperature Plasma Mutagenesis

et al. 2021

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“…The discovery of novel LPs occurs through both top-down and bottom-up approaches. Top-down approaches are based on culture-dependent techniques and screening for bioactivity [127] . Common assays for surfactant activity include the emulsification index [128] , oil spreading and drop collapse methods [129] .…”

Section: Discovery Of New Lps: Where Are We Going?mentioning

confidence: 99%

“…Common assays for surfactant activity include the emulsification index [128] , oil spreading and drop collapse methods [129] . Bottom-up approaches employ advance metagenomics and genomic sequencing combined with new bioinformatics tools for the discovery of genes and enzymes related to LP biosynthesis, such as NRPS and hybrid NRPS-PKS [127] , [130] , [131] . Omics approaches and the advent of high-throughput sequencing tools and powerful bioinformatics pipelines have allowed us to identify the presence and arrangement of biosynthetic gene clusters (BGCs) [132] , [133] .…”

Section: Discovery Of New Lps: Where Are We Going?mentioning

confidence: 99%

The ecological roles of microbial lipopeptides: Where are we going?

Gutiérrez-Chávez

Benaud

Ferrari

2021

Computational and Structural Biotechnology Journal

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Lipopeptides (LPs) are secondary metabolites produced by a diversity of bacteria and fungi. Their unique chemical structure comprises both a peptide and a lipid moiety. LPs are of major biotechnological interest owing to their emulsification, antitumor, immunomodulatory, and antimicrobial activities. To date, these versatile compounds have been applied across multiple industries, from pharmaceuticals through to food processing, cosmetics, agriculture, heavy metal, and hydrocarbon bioremediation. The variety of LP structures and the diversity of the environments from which LP-producing microorganisms have been isolated suggest important functions in their natural environment. However, our understanding of the ecological role of LPs is limited. In this review, the mode of action and the role of LPs in motility, antimicrobial activity, heavy metals removal and biofilm formation are addressed. We include discussion on the need to characterise LPs from a diversity of microorganisms, with a focus on taxa inhabiting ‘extreme’ environments. We introduce the use of computational target fishing and molecular dynamics simulations as powerful tools to investigate the process of interaction between LPs and cell membranes. Together, these advances will provide new understanding of the mechanism of action of novel LPs, providing greater insights into the roles of LPs in the natural environment.

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“…Numbers of methods have been developed to activate silent BGCs in recent years ( Rutledge and Challis, 2015 ; Onaka, 2017 ; Mao et al, 2018 ; Lewis, 2020 ). Powerful bioinformatics approaches for genome mining and identification of NPs BGCs are well summarized in some recent reviews ( Lee et al, 2020 ; Ren et al, 2020 ; Van Santen et al, 2020 ; Kenshole et al, 2021 ). Herein, we provide a concise overview as an introductory guide to the recent advances in silent BGCs activation in Streptomyces from two aspects, involving heterologous reconstruction and in situ activation ( Figure 1 ).…”

Section: Introductionmentioning

confidence: 99%

Recent Advances in Silent Gene Cluster Activation in Streptomyces

Liu

Zhao

Huang

et al. 2021

Front. Bioeng. Biotechnol.

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Natural products (NPs) are critical sources of drug molecules for decades. About two-thirds of natural antibiotics are produced by Streptomyces. Streptomyces have a large number of secondary metabolite biosynthetic gene clusters (SM-BGCs) that may encode NPs. However, most of these BGCs are silent under standard laboratory conditions. Hence, activation of these silent BGCs is essential to current natural products discovery research. In this review, we described the commonly used strategies for silent BGC activation in Streptomyces from two aspects. One focused on the strategies applied in heterologous host, including methods to clone and reconstruct BGCs along with advances in chassis engineering; the other focused on methods applied in native host which includes engineering of promoters, regulatory factors, and ribosomes. With the metabolic network being elucidated more comprehensively and methods optimized more high-thoroughly, the discovery of NPs will be greatly accelerated.

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Mini review: Genome mining approaches for the identification of secondary metabolite biosynthetic gene clusters in Streptomyces

Cited by 129 publications

References 104 publications

Multi-omics Comparative Analysis of Streptomyces Mutants Obtained by Iterative Atmosphere and Room-Temperature Plasma Mutagenesis

Multi-omics Comparative Analysis of Streptomyces Mutants Obtained by Iterative Atmosphere and Room-Temperature Plasma Mutagenesis

The ecological roles of microbial lipopeptides: Where are we going?

Recent Advances in Silent Gene Cluster Activation in Streptomyces

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