scholarly journals Reporter‐Guided Transposon Mutant Selection for Activation of Silent Gene Clusters in Burkholderia thailandensis

ChemBioChem ◽  
2020 ◽  
Vol 21 (13) ◽  
pp. 1826-1831 ◽  
Author(s):  
Dainan Mao ◽  
Aya Yoshimura ◽  
Rurun Wang ◽  
Mohammad R. Seyedsayamdost
Keyword(s):  
Gene Clusters ◽  
Silent Gene ◽  
Mutant Selection ◽  
Burkholderia Thailandensis ◽  
Selection For

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 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.

scholarly journals Malleilactone Is a Burkholderia pseudomallei Virulence Factor Regulated by Antibiotics and Quorum Sensing

2018 ◽  
Vol 200 (14) ◽  
Author(s):  
Jennifer R. Klaus ◽  
Jacqueline Deay ◽  
Benjamin Neuenswander ◽  
Wyatt Hursh ◽  
Zhe Gao ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Caenorhabditis Elegans ◽  
Quorum Sensing ◽  
Virulence Factor ◽  
Mammalian Cells ◽  
Burkholderia Pseudomallei ◽  
Gene Clusters ◽  
Close Relative ◽  
Burkholderia Thailandensis ◽  
Content Type

ABSTRACT Burkholderia pseudomallei , the causative agent of melioidosis, encodes almost a dozen predicted polyketide (PK) biosynthetic gene clusters. Many of these are regulated by LuxR-I-type acyl-homoserine (AHL) quorum-sensing systems. One of the PK gene clusters, the mal gene cluster, is conserved in the close relative Burkholderia thailandensis . The B. thailandensis mal genes code for the cytotoxin malleilactone and are regulated by a genetically linked LuxR-type transcription factor, MalR. Although AHLs typically interact with LuxR-type proteins to modulate gene transcription, the B. thailandensis MalR does not appear to be an AHL receptor. Here, we characterize the mal genes and MalR in B. pseudomallei . We use chemical analyses to demonstrate that the B. pseudomallei mal genes code for malleilactone. Our results show that MalR and the mal genes contribute to the ability of B. pseudomallei to kill Caenorhabditis elegans . In B. thailandensis , antibiotics like trimethoprim can activate MalR by driving transcription of the mal genes, and we demonstrate that some of the same antibiotics induce expression of B. pseudomallei malR . We also demonstrate that B. pseudomallei MalR does not respond directly to AHLs. Our results suggest that MalR is indirectly repressed by AHLs, possibly through a repressor, ScmR. We further show that malleilactone is a B. pseudomallei virulence factor and provide the foundation for understanding how malleilactone contributes to the pathology of melioidosis infections. IMPORTANCE Many bacterially produced polyketides are cytotoxic to mammalian cells and are potentially important contributors to pathogenesis during infection. We are interested in the polyketide gene clusters present in Burkholderia pseudomallei , which causes the often-fatal human disease melioidosis. Using knowledge gained by studies in the close relative Burkholderia thailandensis , we show that one of the B. pseudomallei polyketide biosynthetic clusters produces a cytotoxic polyketide, malleilactone. Malleilactone contributes to B. pseudomallei virulence in a Caenorhabditis elegans infection model and is regulated by an orphan LuxR family quorum-sensing transcription factor, MalR. Our studies demonstrate that malleilactone biosynthesis or MalR could be new targets for developing therapeutics to treat melioidosis.

scholarly journals Generation and initial characterization of a collection of spontaneous Streptomyces albus J1074 mutants resistant to rifampicin

2020 ◽  
Vol 27 ◽  
pp. 139-143
Author(s):  
B. O. Ostash ◽  
Yu. Misaki ◽  
B. S. Dolya ◽  
Ya. I. Kharaton ◽  
T. Busche ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Wide Spectrum ◽  
Gene Clusters ◽  
Antibiotic Activity ◽  
Missense Mutations ◽  
Resistance Mutations ◽  
Resistance Level ◽  
Streptomyces Albus ◽  
Selection For ◽  
Streptomyces Albus J1074

Aim. Streptomyces albus J1074 is one of the most popular streptomycete chassis for heterologous expression of natural product (NP) biosynthetic gene clusters (BGCs). There is keen interest in further improvement of the strain to provide increased yields of corresponding NPs. Introduction of certain types of antibiotic resistance mutations is a proven way to improve Streptomyces strains. For example, selection for increased resistance to rifampicin is known to lead to increased antibiotic activity. Here we used available lineages of antibiotic-resistant mutants of S. albus to raise rifampicin-resistant variants (Rifr) and to study their properties. Methods. Microbiological and molecular genetic approaches were combined to generate Rifr mutants and to study their properties. Results. By plating S. albus onto GYM agar supplemented with 10 mcg/mL of rifampicin, we isolated 85 stable Rifr colonies, whose resistance level was within 10-200 mcg/mL range. Sequencing revealed wide spectrum of missense mutations within rpoB gene. Bioassays demonstrated dramatically increased endogenous antibiotic activity of certain Rifr mutants. Conclusions. Selection for rifampicin resistance is a viable way to increase the yields of NPs in S. albus. Keywords: Streptomyces albus J1074, antibiotic resistance, rifampicin.

scholarly journals Burkholderia thailandensis harbors two identical rhl gene clusters responsible for the biosynthesis of rhamnolipids

2009 ◽  
Vol 9 (1) ◽  
pp. 263 ◽  
Author(s):  
Danielle Dubeau ◽  
Eric Déziel ◽  
Donald E Woods ◽  
François Lépine
Keyword(s):  
Gene Clusters ◽  
Burkholderia Thailandensis

scholarly journals A NEW METHOD FOR MUTANT SELECTION IN SACCHAROMYCES CEREVISIAE

Genetics ◽  
1975 ◽  
Vol 79 (2) ◽  
pp. 175-186
Author(s):  
Susan A Henry ◽  
Bernard Horowitz
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Fatty Acid ◽  
Fold Increase ◽  
New Method ◽  
Temperature Sensitive ◽  
Macromolecular Synthesis ◽  
Mutant Selection ◽  
Temperature Sensitive Mutants ◽  
Selection For ◽  
Selection Of

ABSTRACT A new method for the selection of auxotrophic, antibiotic- and temperature-sensitive mutants in Saccharomyces cerevisiae is reported. The technique is based upon the observation that certain fatty acid auxotrophs of yeast die when deprived of fatty acid only under conditions supporting growth. When macromolecular synthesis is blocked, the fatty acid-starved cells survive. By appropriate manipulation of a fatty acid-requiring strain enrichment as great as 75-fold was achieved for certain classes of auxotrophic mutants. An enrichment of approximately 100-fold is possible for some antibiotic-sensitive mutants. Selection for temperature-sensitive mutants, however, resulted in less than a 2-fold increase in the frequency of such mutants, probably because of the heterogeneity of this mutant category. It is likely that only that fraction of temperature-sensitive mutations which rapidly and reversibly blocks macromolecular synthesis is selected by this technique.

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.

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