scholarly journals Discovery of Two New Sorbicillinoids by Overexpression of the Global Regulator LaeA in a Marine-Derived Fungus Penicillium dipodomyis YJ-11

Marine Drugs ◽  
2019 ◽  
Vol 17 (8) ◽  
pp. 446 ◽  
Author(s):  
Jing Yu ◽  
Huan Han ◽  
Xianyan Zhang ◽  
Chuanteng Ma ◽  
Chunxiao Sun ◽  
...  
Keyword(s):  
Mutant Strain ◽  
Morphological Changes ◽  
Gene Clusters ◽  
Fungal Strain ◽  
Chemical Investigation ◽  
Global Regulator ◽  
Silent Gene

Overexpression of the global regulator LaeA in a marine-derived fungal strain of Penicillium dipodomyis YJ-11 induced obvious morphological changes and metabolic variations. Further chemical investigation of the mutant strain afforded a series of sorbicillinoids including two new ones named 10,11-dihydrobislongiquinolide (1) and 10,11,16,17-tetrahydrobislongiquinolide (2), as well as four known analogues, bislongiquinolide (3), 16,17-dihydrobislongiquinolide (4), sohirnone A (5), and 2′,3′-dihydrosorbicillin (6). The results support that the global regulator LaeA is a useful tool in activating silent gene clusters in Penicillium strains to obtain previously undiscovered compounds.

Activation of fungal silent gene clusters: A new avenue to drug discovery

2008 ◽  
pp. 1-12 ◽  
Author(s):  
Axel A. Brakhage ◽  
Julia Schuemann ◽  
Sebastian Bergmann ◽  
Kirstin Scherlach ◽  
Volker Schroeckh ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Gene Clusters ◽  
Silent Gene

scholarly journals Activation and enhancement of Caerulomycin A biosynthesis in marine-derived Actinoalloteichus sp. AHMU CJ021 by combinatorial genome mining strategies

2020 ◽  
Author(s):  
Yunchang Xie ◽  
Jiawen Chen ◽  
Bo Wang ◽  
Tai Chen ◽  
Junyu Chen ◽  
...  
Keyword(s):  
Natural Products ◽  
Mutant Strain ◽  
Genome Mining ◽  
Gene Clusters ◽  
Immunosuppressive Drug ◽  
Biosynthetic Gene ◽  
Bioactive Natural Products ◽  
Drug Lead ◽  
A Genome ◽  
Mining Work

Abstract Backgrounds: Activation of silent biosynthetic gene clusters (BGCs) in marine-derived actinomycete strains is a feasible strategy to discover bioactive natural products. Actinoalloteichus sp. AHMU CJ021, isolated from the seashore, was shown to contain an intact but silent caerulomycin A (CRM A) BGC-cam in its genome. Thus, a genome mining work was preformed to activate the strain’s bioproduction of CRM A, an immunosuppressive drug lead with diverse bioactivities.Results: To well activate the expression of cam, ribosomal engineering was adopted to treat the wild type Actinoalloteichus sp. AHMU CJ021. The initial mutant strain XC-11G with gentamycin resistance and CRM A bioproduction titer of 42.51 ± 4.22 mg/L was selected from all generated mutant strains by gene expression comparison of the essential biosynthetic gene-camE. The titer of CRM A bioproduction was then improved by two strain breeding methods via UV mutagenesis and cofactor engineering-directed increasing of intracellular riboflavin, which finally generated the optimal mutant strain XC-11GUR with a CRM A bioproduction titer of 113.91 ± 7.58 mg/L. Subsequently, this titer of strain XC-11GUR was improved to 618.61 ± 16.29 mg/L through medium optimization together with further adjustment derived from response surface methodology. In terms of this 14.7 folds increase in the titer of CRM A compared to the initial value, strain XC-GUR could be a well alternative strain for CRM A development.Conclusions: Our results have constructed an ideal CRM A producer. More importantly, our efforts also have demonstrated the effectiveness of abovementioned combinatorial strategies, which is applicable to the genome mining of bioactive natural products from abundant actinomycetes strains.

scholarly journals Activation and enhancement of Caerulomycin A biosynthesis in marine-derived Actinoalloteichus sp. AHMU CJ021 by combinatorial genome mining strategies

2020 ◽  
Author(s):  
Yunchang Xie ◽  
Jiawen Chen ◽  
Bo Wang ◽  
Tai Chen ◽  
Junyu Chen ◽  
...  
Keyword(s):  
Natural Products ◽  
Mutant Strain ◽  
Genome Mining ◽  
Gene Clusters ◽  
Immunosuppressive Drug ◽  
Biosynthetic Gene ◽  
Bioactive Natural Products ◽  
Drug Lead ◽  
A Genome ◽  
Mining Work

Abstract Backgrounds: Activation of silent biosynthetic gene clusters (BGCs) in marine-derived actinomycete strains is a feasible strategy to discover bioactive natural products. Actinoalloteichus sp. AHMU CJ021, isolated from the seashore, was shown to contain an intact but silent caerulomycin A (CRM A) BGC-cam in its genome. Thus, a genome mining work was preformed to activate the strain’s production of CRM A, an immunosuppressive drug lead with diverse bioactivities.Results: To well activate the expression of cam, ribosome engineering was adopted to treat the wild type Actinoalloteichus sp. AHMU CJ021. The initial mutant strain XC-11G with gentamycin resistance and CRM A production titer of 42.51 ± 4.22 mg/L was selected from all generated mutant strains by gene expression comparison of the essential biosynthetic gene-camE. The titer of CRM A production was then improved by two strain breeding methods via UV mutagenesis and cofactor engineering-directed increase of intracellular riboflavin, which finally generated the optimal mutant strain XC-11GUR with a CRM A production titer of 113.91 ± 7.58 mg/L. Subsequently, this titer of strain XC-11GUR was improved to 618.61 ± 16.29 mg/L through medium optimization together with further adjustment derived from response surface methodology. In terms of this 14.6 folds increase in the titer of CRM A compared to the initial value, strain XC-GUR could be a well alternative strain for CRM A development.Conclusions: Our results have constructed an ideal CRM A producer. More importantly, our efforts also have demonstrated the effectiveness of abovementioned combinatorial strategies, which is applicable to the genome mining of bioactive natural products from abundant actinomycetes strains.

scholarly journals Activation and enhancement of Caerulomycin A biosynthesis in marine-derived Actinoalloteichus sp. AHMU CJ021 by combinatorial genome mining strategies

2020 ◽  
Author(s):  
Yunchang Xie ◽  
Jiawen Chen ◽  
Bo Wang ◽  
Tai Chen ◽  
Junyu Chen ◽  
...  
Keyword(s):  
Natural Products ◽  
Mutant Strain ◽  
Genome Mining ◽  
Gene Clusters ◽  
Immunosuppressive Drug ◽  
Biosynthetic Gene ◽  
Bioactive Natural Products ◽  
Drug Lead ◽  
A Genome ◽  
Mining Work

Abstract Backgrounds: Activation of silent biosynthetic gene clusters (BGCs) in marine-derived actinomycete strains is a feasible strategy to discover bioactive natural products. Actinoalloteichus sp. AHMU CJ021, isolated from the seashore, was shown to contain an intact but silent caerulomycin A (CRM A) BGC- cam in its genome. Thus, a genome mining work was preformed to activate the strain’s production of CRM A, an immunosuppressive drug lead with diverse bioactivities.Results: To well activate the expression of cam , ribosome engineering was adopted to treat the wild type Actinoalloteichus sp. AHMU CJ021. The initial mutant strain XC-11G with gentamycin resistance and CRM A production titer of 42.51 ± 4.22 mg/L was selected from all generated mutant strains by gene expression comparison of the essential biosynthetic gene-camE. The titer of CRM A production was then improved by two strain breeding methods via UV mutagenesis and cofactor engineering-directed increase of intracellular riboflavin, which finally generated the optimal mutant strain XC-11GUR with a CRM A production titer of 113.91 ± 7.58 mg/L. Subsequently, this titer of strain XC-11GUR was improved to 618.61 ± 16.29 mg/L through medium optimization together with further adjustment derived from response surface methodology. In terms of this 14.6 folds increase in the titer of CRM A compared to the initial value, strain XC-GUR could be a well alternative strain for CRM A development.Conclusions: Our results have constructed an ideal CRM A producer. More importantly, our efforts also have demonstrated the effectiveness of abovementioned combinatorial strategies, which is applicable to the genome mining of bioactive natural products from abundant actinomycetes strains.

scholarly journals Targeted induction of a silent fungal gene cluster encoding the bacteria-specific germination inhibitor fumigermin

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Maria Cristina Stroe ◽  
Tina Netzker ◽  
Kirstin Scherlach ◽  
Thomas Krüger ◽  
Christian Hertweck ◽  
...  
Keyword(s):  
Gene Cluster ◽  
Polyketide Synthase ◽  
Biological Activities ◽  
Gene Clusters ◽  
Ecological Function ◽  
The Novel ◽  
Ecological Context ◽  
Fungal Metabolite ◽  
Silent Gene ◽  
Encoding Gene

Microorganisms produce numerous secondary metabolites (SMs) with various biological activities. Many of their encoding gene clusters are silent under standard laboratory conditions because for their activation they need the ecological context, such as the presence of other microorganisms. The true ecological function of most SMs remains obscure, but understanding of both the activation of silent gene clusters and the ecological function of the produced compounds is of importance to reveal functional interactions in microbiomes. Here, we report the identification of an as-yet uncharacterized silent gene cluster of the fungus Aspergillus fumigatus, which is activated by the bacterium Streptomyces rapamycinicus during the bacterial-fungal interaction. The resulting natural product is the novel fungal metabolite fumigermin, the biosynthesis of which requires the polyketide synthase FgnA. Fumigermin inhibits germination of spores of the inducing S. rapamycinicus, and thus helps the fungus to defend resources in the shared habitat against a bacterial competitor.

scholarly journals Recent Advances in Silent Gene Cluster Activation in Streptomyces

2021 ◽  
Vol 9 ◽  
Author(s):  
Zhenyu Liu ◽  
Yatong Zhao ◽  
Chaoqun Huang ◽  
Yunzi Luo
Keyword(s):  
Natural Products ◽  
Gene Clusters ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Heterologous Host ◽  
Silent Gene ◽  
Drug Molecules ◽  
Discovery Research ◽  
Natural Products Discovery ◽  
Native Host

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.

scholarly journals Global Stage-Specific Gene Regulation during the Developmental Cycle of Chlamydia trachomatis

2003 ◽  
Vol 185 (10) ◽  
pp. 3179-3189 ◽  
Author(s):  
Tracy L. Nicholson ◽  
Lynn Olinger ◽  
Kimberley Chong ◽  
Gary Schoolnik ◽  
Richard S. Stephens
Keyword(s):  
Gene Regulation ◽  
Chlamydia Trachomatis ◽  
Morphological Changes ◽  
Bacterial Pathogen ◽  
Gene Clusters ◽  
Specific Gene ◽  
Developmental Cycle ◽  
Transcriptional Level ◽  
Development Cycle ◽  
Complex Development

ABSTRACT Distinct morphological changes associated with the complex development cycle of the obligate intracellular bacterial pathogen Chlamydia trachomatis have been historically well characterized by microscopy. A number of temporally regulated genes have been characterized previously, suggesting that the chlamydial developmental cycle is regulated at the transcriptional level. This hypothesis was tested by microarray analysis in which the entire C. trachomatis genome was analyzed, providing a comprehensive assessment of global gene regulation throughout the chlamydial developmental cycle. Seven temporally cohesive gene clusters were identified, with 22% (189 genes) of the genome differentially expressed during the developmental cycle. The correlation of these gene clusters with hallmark morphological events of the chlamydial developmental cycle suggests three global stage-specific networks of gene regulation.

scholarly journals Warum Mikroorganismen Naturstoffe produzieren

BIOspektrum ◽  
2020 ◽  
Vol 26 (7) ◽  
pp. 731-733
Author(s):  
Mario K. C. Krespach ◽  
Maria C. Stroe ◽  
Axel A. Brakhage
Keyword(s):  
Natural Products ◽  
Gene Clusters ◽  
Ecological Function ◽  
Microbial Interactions ◽  
Standard Laboratory ◽  
Silent Gene ◽  
Laboratory Conditions ◽  
Encoding Gene

AbstractA key role in the communication between fungi and bacteria is played by natural products. Many of their encoding gene clusters are silent under standard laboratory conditions. Interspecies “talk” between microorganisms represents an ecological trigger to activate such silent gene clusters and leads to the formation of novel natural products by the involved species. The understanding of both the activation of silent gene clusters and the ecological function of the produced compounds is of importance to reveal functional microbial interactions required to shape microbiomes.

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