Strategies to establish the link between biosynthetic gene clusters and secondary metabolites

Inge Kjærbølling, Uffe H. Mortensen, Tammi Vesth, Mikael R. Andersen*

*Corresponding author for this work

Research output: Contribution to journalReviewResearchpeer-review

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Abstract

Filamentous fungi produce a vast number of bioactive secondary metabolites (SMs), some of which have found applications in the pharmaceutical industry including as antibiotics and immunosuppressants. As more and more species are whole genome sequenced the number of predicted clusters of genes for SM biosynthesis is ever increasing – holding a promise of novel useful bioactive SMs. To be able to fully utilize the potential of novel SMs, it is necessary to link the SM and the genes responsible for producing it. This can be challenging, but many strategies and tools have been developed for this purpose. Here we provide an overview of the methods used to establish the link between SM and biosynthetic gene cluster (BGC) and vice versa, along with the challenges and advantages of each of the methods. Part I of the review, associating BCG with SM, is divided into gene manipulations native strain and heterologous expression strategies, depending on the fungal species. Part II, associating SM with BGC, is divided into three main approaches: (1) homology search (2) retro-biosynthesis and (3) comparative genomics.

Original languageEnglish
JournalFungal Genetics and Biology
Volume130
Pages (from-to)107-121
Number of pages15
ISSN1087-1845
DOIs
Publication statusPublished - 2019

Keywords

  • Biosynthetic gene clusters
  • Filamentous fungi
  • Nonribosomal peptide synthetase
  • Polyketide synthase
  • Secondary metabolites

Cite this

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title = "Strategies to establish the link between biosynthetic gene clusters and secondary metabolites",
abstract = "Filamentous fungi produce a vast number of bioactive secondary metabolites (SMs), some of which have found applications in the pharmaceutical industry including as antibiotics and immunosuppressants. As more and more species are whole genome sequenced the number of predicted clusters of genes for SM biosynthesis is ever increasing – holding a promise of novel useful bioactive SMs. To be able to fully utilize the potential of novel SMs, it is necessary to link the SM and the genes responsible for producing it. This can be challenging, but many strategies and tools have been developed for this purpose. Here we provide an overview of the methods used to establish the link between SM and biosynthetic gene cluster (BGC) and vice versa, along with the challenges and advantages of each of the methods. Part I of the review, associating BCG with SM, is divided into gene manipulations native strain and heterologous expression strategies, depending on the fungal species. Part II, associating SM with BGC, is divided into three main approaches: (1) homology search (2) retro-biosynthesis and (3) comparative genomics.",
keywords = "Biosynthetic gene clusters, Filamentous fungi, Nonribosomal peptide synthetase, Polyketide synthase, Secondary metabolites",
author = "Inge Kj{\ae}rb{\o}lling and Mortensen, {Uffe H.} and Tammi Vesth and Andersen, {Mikael R.}",
year = "2019",
doi = "10.1016/j.fgb.2019.06.001",
language = "English",
volume = "130",
pages = "107--121",
journal = "Fungal Genetics and Biology",
issn = "1087-1845",
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Strategies to establish the link between biosynthetic gene clusters and secondary metabolites. / Kjærbølling, Inge; Mortensen, Uffe H.; Vesth, Tammi; Andersen, Mikael R.

In: Fungal Genetics and Biology, Vol. 130, 2019, p. 107-121.

Research output: Contribution to journalReviewResearchpeer-review

TY - JOUR

T1 - Strategies to establish the link between biosynthetic gene clusters and secondary metabolites

AU - Kjærbølling, Inge

AU - Mortensen, Uffe H.

AU - Vesth, Tammi

AU - Andersen, Mikael R.

PY - 2019

Y1 - 2019

N2 - Filamentous fungi produce a vast number of bioactive secondary metabolites (SMs), some of which have found applications in the pharmaceutical industry including as antibiotics and immunosuppressants. As more and more species are whole genome sequenced the number of predicted clusters of genes for SM biosynthesis is ever increasing – holding a promise of novel useful bioactive SMs. To be able to fully utilize the potential of novel SMs, it is necessary to link the SM and the genes responsible for producing it. This can be challenging, but many strategies and tools have been developed for this purpose. Here we provide an overview of the methods used to establish the link between SM and biosynthetic gene cluster (BGC) and vice versa, along with the challenges and advantages of each of the methods. Part I of the review, associating BCG with SM, is divided into gene manipulations native strain and heterologous expression strategies, depending on the fungal species. Part II, associating SM with BGC, is divided into three main approaches: (1) homology search (2) retro-biosynthesis and (3) comparative genomics.

AB - Filamentous fungi produce a vast number of bioactive secondary metabolites (SMs), some of which have found applications in the pharmaceutical industry including as antibiotics and immunosuppressants. As more and more species are whole genome sequenced the number of predicted clusters of genes for SM biosynthesis is ever increasing – holding a promise of novel useful bioactive SMs. To be able to fully utilize the potential of novel SMs, it is necessary to link the SM and the genes responsible for producing it. This can be challenging, but many strategies and tools have been developed for this purpose. Here we provide an overview of the methods used to establish the link between SM and biosynthetic gene cluster (BGC) and vice versa, along with the challenges and advantages of each of the methods. Part I of the review, associating BCG with SM, is divided into gene manipulations native strain and heterologous expression strategies, depending on the fungal species. Part II, associating SM with BGC, is divided into three main approaches: (1) homology search (2) retro-biosynthesis and (3) comparative genomics.

KW - Biosynthetic gene clusters

KW - Filamentous fungi

KW - Nonribosomal peptide synthetase

KW - Polyketide synthase

KW - Secondary metabolites

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DO - 10.1016/j.fgb.2019.06.001

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EP - 121

JO - Fungal Genetics and Biology

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SN - 1087-1845

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