scholarly journals Resistance Gene-Directed Genome Mining of 50 Aspergillus Species

mSystems ◽  
2019 ◽  
Vol 4 (4) ◽  
Author(s):  
Inge Kjærbølling ◽  
Tammi Vesth ◽  
Mikael R. Andersen

Species belonging to the Aspergillus genus are known to produce a large number of secondary metabolites; some of these compounds are used as pharmaceuticals, such as penicillin, cyclosporine, and statin. With whole-genome sequencing, it became apparent that the genetic potential for secondary metabolite production is much larger than expected. As an increasing number of species are whole-genome sequenced, thousands of secondary metabolite genes are predicted, and the question of how to selectively identify novel bioactive compounds from this information arises. To address this question, we have created a pipeline to predict genes involved in the production of bioactive compounds based on a resistance gene hypothesis approach.

2020 ◽  
Vol 37 (9) ◽  
pp. 1164-1180 ◽  
Author(s):  
Liwen Zhang ◽  
Qun Yue ◽  
Chen Wang ◽  
Yuquan Xu ◽  
István Molnár

Whole genome sequencing allows the cataloguing of the parvome (secondary metabolome) of hypocrealean entomopathogenic fungi, uncovering biosynthetic gene clusters for known and novel bioactive compounds with ecological and pharmaceutical significance.


2018 ◽  
Author(s):  
Inge Kjærbølling ◽  
Tammi Vesth ◽  
Mikael R. Andersen

AbstractFungal secondary metabolites are a rich source of valuable natural products. Genome sequencing have revealed an enormous potential from predicted biosynthetic gene clusters. It is however currently a time consuming task and an unfeasible task to characterize all biosynthetic gene cluster and to identify possible uses of the compounds. A rational approach is needed to identify promising gene clusters responsible for producing valuable compounds. Several valuable bioactive clusters have been shown to include a resistance gene which is a paralog of the target gene inhibited by the compound. This mechanism can be used to design a rational approach selecting those clusters.We have developed a pipeline FRIGG (Fungal Resistance Gene-directed Genome mining) identifying putative resistance genes found in biosynthetic gene clusters based on homology patterns of the cluster genes. The FRIGG pipeline has been run using 51 Aspergillus and Penicillium genomes, identifying 72 unique protein families with putative resistance genes using various settings in the pipeline. The pipeline was also able to identify the characterized resistance gene inpE from the Fellutamide B cluster thereby validating the approach.We have successfully developed an approach identifying putative valuable bio-active clusters based on a specific resistance mechanism. This approach will be highly useful as an ever increasing amount of genomic data becomes available — the art of identifying and selecting clusters producing novel valuable compounds will only become more crucial.ImportanceSpecies belonging to the Aspergillus genus are known to produce a large number of secondary metabolites, some of these compounds are bioactive and used as pharmaceuticals such as penicillin, cyclosporin and statin. With whole genome sequencing it became apparent that the genetic potential for secondary metabolite production is much bigger than expected. As an increasing number of species are whole genome sequenced an immense number of secondary metabolite genes are predicted and the question of how to selectively identify novel bioactive compounds from this information arises. To address this question, we have created a pipeline identifying genes likely involved in the production of bioactive compounds based on a resistance gene hypothesis approach.


Genomics ◽  
2020 ◽  
Vol 112 (5) ◽  
pp. 2915-2921 ◽  
Author(s):  
Thiago Mafra Batista ◽  
Heron Oliveira Hilario ◽  
Gabriel Antônio Mendes de Brito ◽  
Rennan Garcias Moreira ◽  
Carolina Furtado ◽  
...  

2015 ◽  
Vol 68 (10) ◽  
pp. 835-838 ◽  
Author(s):  
Björn A Espedido ◽  
Borce Dimitrijovski ◽  
Sebastiaan J van Hal ◽  
Slade O Jensen

AimsTo characterise the resistome of a multi-drug resistant Klebsiella pneumoniae (Kp0003) isolated from an Australian traveller who was repatriated to a Sydney Metropolitan Hospital from Myanmar with possible prosthetic aortic valve infective endocarditis.MethodsKp0003 was recovered from a blood culture of the patient and whole genome sequencing was performed. Read mapping and de novo assembly of reads facilitated in silico multi-locus sequence and plasmid replicon typing as well as the characterisation of antibiotic resistance genes and their genetic context. Conjugation experiments were also performed to assess the plasmid (and resistance gene) transferability and the effect on the antibiotic resistance phenotype.ResultsImportantly, and of particular concern, the carbapenem-hydrolysing β-lactamase gene blaNDM-4 was identified on a conjugative IncX3 plasmid (pJEG027). In this respect, the blaNDM-4 genetic context is similar (at least to some extent) to what has previously been identified for blaNDM-1 and blaNDM-4-like variants.ConclusionsThis study highlights the potential role that IncX3 plasmids have played in the emergence and dissemination of blaNDM-4-like variants worldwide and emphasises the importance of resistance gene surveillance.


2021 ◽  
Author(s):  
Krishna Kumar Rai ◽  
Nagendra Rai ◽  
Shashi Pandey-Rai

Hyacinth bean also known as Indian bean is multipurpose legume crops consumed both as food by humans and as forage by animals. Being a rich source of protein, it also produces distinct secondary metabolites such as flavonoids, phenols and tyrosinase which not only help strengthened plant’s own innate immunity against abiotic/biotrophic attackers but also play important therapeutic role in the treatment of various chronic diseases. However, despite its immense therapeutic and nutritional attributes in strengthening food, nutrition and therapeutic security in many developing countries, it is still considered as an “orphan crop” for unravelling its genetic potential and underlying molecular mechanisms for enhancing secondary metabolite production. Several lines of literatures have well documented the use of OMICS based techniques and biotic and abiotic elicitors for stimulating secondary metabolite production particularly in model as well as in few economically important crops. However, only limited reports have described their application for stimulating secondary metabolite production in underutilised crops. Therefore, the present chapter will decipher different dimensions of multi-omics tools and their integration with other conventional techniques (biotic and abiotic elicitors) for unlocking hidden genetic potential of hyacinth bean for elevating the production of secondary metabolites having pharmaceutical and therapeutic application. Additionally, the study will also provide valuable insights about how these advance OMICS tools can be successfully exploited for accelerating functional genomics and breeding research for unravelling their hidden pharmaceutical and therapeutic potential thereby ensuring food and therapeutic security for the betterment of mankind.


2013 ◽  
Vol 4 (1) ◽  
Author(s):  
Emma S. Mace ◽  
Shuaishuai Tai ◽  
Edward K. Gilding ◽  
Yanhong Li ◽  
Peter J. Prentis ◽  
...  

Marine Drugs ◽  
2021 ◽  
Vol 19 (6) ◽  
pp. 332
Author(s):  
Dini Hu ◽  
Simon Ming-Yuen Lee ◽  
Kai Li ◽  
Kai Meng Mok

Mangroves are intertidal extreme environments with rich microbial communities. Actinobacteria are well known for producing antibiotics. The search for biosynthetic potential of Actinobacteria from mangrove environments could provide more possibilities for useful secondary metabolites. In this study, whole genome sequencing and MS/MS analysis were used to explore the secondary metabolite production potential of one actinobacterial strain of Streptomyces olivaceus sp., isolated from a mangrove in Macau, China. The results showed that a total of 105 gene clusters were found in the genome of S. olivaceus sp., and 53 known secondary metabolites, including bioactive compounds, peptides, and other products, were predicted by genome mining. There were 28 secondary metabolites classified as antibiotics, which were not previously known from S. olivaceus. ISP medium 2 was then used to ferment the S. olivaceus sp. to determine which predicted secondary metabolite could be truly produced. The chemical analysis revealed that ectoine, melanin, and the antibiotic of validamycin A could be observed in the fermentation broth. This was the first observation that these three compounds can be produced by a strain of S. olivaceus. Therefore, it can be concluded that Actinobacteria isolated from the mangrove environment have unknown potential to produce bioactive secondary metabolites.


2015 ◽  
Vol 59 (8) ◽  
pp. 5022-5025 ◽  
Author(s):  
Yanbin Liu ◽  
Yu Feng ◽  
Wenjing Wu ◽  
Yi Xie ◽  
Xiaohui Wang ◽  
...  

ABSTRACTWe report the first OXA-181-producing strain in China.blaOXA-181was found in sequence type 410 (ST410)Escherichia colistrain WCHEC14828 from a Chinese patient without recent travel history. Genome sequencing and conjugation experiments were performed.blaOXA-181was carried on a 51-kb self-transmissible IncX3 plasmid and was linked withqnrS1, a quinolone resistance gene.blaOXA-181was introduced onto the IncX3 plasmid from a ColE2-type plasmid, and IncX3 plasmids have the potential to mediate the dissemination ofblaOXA-181.


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