Genomics‐Guided Efficient Identification of 2,5‐Diketopiperazine Derivatives from Actinobacteria
Secondary metabolites derived from microorganism constitute an important part of natural products. Mining of the microbial genomes revealed a large number of uncharacterized biosynthetic gene clusters, indicating their greater potential to synthetize specialized or secondary metabolites (SMs) than i...
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| Published in | Chembiochem : a European journal of chemical biology Vol. 24; no. 3; pp. e202200502 - n/a |
|---|---|
| Main Authors | , |
| Format | Journal Article |
| Language | English |
| Published |
Germany
Wiley Subscription Services, Inc
01.02.2023
John Wiley and Sons Inc |
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| Online Access | Get full text |
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| Abstract | Secondary metabolites derived from microorganism constitute an important part of natural products. Mining of the microbial genomes revealed a large number of uncharacterized biosynthetic gene clusters, indicating their greater potential to synthetize specialized or secondary metabolites (SMs) than identified by classic fermentation and isolation approaches. Various bioinformatics tools have been developed to analyze and identify such gene clusters, thus accelerating significantly the mining process. Heterologous expression of an individual biosynthetic gene cluster has been proven as an efficient way to activate the genes and identify the encoded metabolites that cannot be detected under normal laboratory cultivation conditions. Herein, we describe a concept of genomics‐guided approach by performing genome mining and heterologous expression to uncover novel CDPS‐derived DKPs and functionally characterize novel tailoring enzymes embedded in the biosynthetic pathways. Recent works focused on the identification of the nucleobase‐related and dimeric DKPs are also presented.
Genome mining combined with heterologous expression has been demonstrated to be an efficient way to identify novel 2,5‐diketopiperazine derivatives from actinobacteria. Meanwhile, their biosynthetic pathways and new enzymes embedded inside have been functionally characterized. It is expected that more biologically active diketopiperazines can be obtained by exploring the genetic potentials of microorganism in the future. |
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| AbstractList | Secondary metabolites derived from microorganism constitute an important part of natural products. Mining of the microbial genomes revealed a large number of uncharacterized biosynthetic gene clusters, indicating their greater potential to synthetize specialized or secondary metabolites (SMs) than identified by classic fermentation and isolation approaches. Various bioinformatics tools have been developed to analyze and identify such gene clusters, thus accelerating significantly the mining process. Heterologous expression of an individual biosynthetic gene cluster has been proven as an efficient way to activate the genes and identify the encoded metabolites that cannot be detected under normal laboratory cultivation conditions. Herein, we describe a concept of genomics-guided approach by performing genome mining and heterologous expression to uncover novel CDPS-derived DKPs and functionally characterize novel tailoring enzymes embedded in the biosynthetic pathways. Recent works focused on the identification of the nucleobase-related and dimeric DKPs are also presented.Secondary metabolites derived from microorganism constitute an important part of natural products. Mining of the microbial genomes revealed a large number of uncharacterized biosynthetic gene clusters, indicating their greater potential to synthetize specialized or secondary metabolites (SMs) than identified by classic fermentation and isolation approaches. Various bioinformatics tools have been developed to analyze and identify such gene clusters, thus accelerating significantly the mining process. Heterologous expression of an individual biosynthetic gene cluster has been proven as an efficient way to activate the genes and identify the encoded metabolites that cannot be detected under normal laboratory cultivation conditions. Herein, we describe a concept of genomics-guided approach by performing genome mining and heterologous expression to uncover novel CDPS-derived DKPs and functionally characterize novel tailoring enzymes embedded in the biosynthetic pathways. Recent works focused on the identification of the nucleobase-related and dimeric DKPs are also presented. Secondary metabolites derived from microorganism constitute an important part of natural products. Mining of the microbial genomes revealed a large number of uncharacterized biosynthetic gene clusters, indicating their greater potential to synthetize specialized or secondary metabolites (SMs) than identified by classic fermentation and isolation approaches. Various bioinformatics tools have been developed to analyze and identify such gene clusters, thus accelerating significantly the mining process. Heterologous expression of an individual biosynthetic gene cluster has been proven as an efficient way to activate the genes and identify the encoded metabolites that cannot be detected under normal laboratory cultivation conditions. Herein, we describe a concept of genomics‐guided approach by performing genome mining and heterologous expression to uncover novel CDPS‐derived DKPs and functionally characterize novel tailoring enzymes embedded in the biosynthetic pathways. Recent works focused on the identification of the nucleobase‐related and dimeric DKPs are also presented. Secondary metabolites derived from microorganism constitute an important part of natural products. Mining of the microbial genomes revealed a large number of uncharacterized biosynthetic gene clusters, indicating their greater potential to synthetize specialized or secondary metabolites (SMs) than identified by classic fermentation and isolation approaches. Various bioinformatics tools have been developed to analyze and identify such gene clusters, thus accelerating significantly the mining process. Heterologous expression of an individual biosynthetic gene cluster has been proven as an efficient way to activate the genes and identify the encoded metabolites that cannot be detected under normal laboratory cultivation conditions. Herein, we describe a concept of genomics‐guided approach by performing genome mining and heterologous expression to uncover novel CDPS‐derived DKPs and functionally characterize novel tailoring enzymes embedded in the biosynthetic pathways. Recent works focused on the identification of the nucleobase‐related and dimeric DKPs are also presented. Genome mining combined with heterologous expression has been demonstrated to be an efficient way to identify novel 2,5‐diketopiperazine derivatives from actinobacteria. Meanwhile, their biosynthetic pathways and new enzymes embedded inside have been functionally characterized. It is expected that more biologically active diketopiperazines can be obtained by exploring the genetic potentials of microorganism in the future. Secondary metabolites derived from microorganism constitute an important part of natural products. Mining of the microbial genomes revealed a large number of uncharacterized biosynthetic gene clusters, indicating their greater potential to synthetize specialized or secondary metabolites (SMs) than identified by classic fermentation and isolation approaches. Various bioinformatics tools have been developed to analyze and identify such gene clusters, thus accelerating significantly the mining process. Heterologous expression of an individual biosynthetic gene cluster has been proven as an efficient way to activate the genes and identify the encoded metabolites that cannot be detected under normal laboratory cultivation conditions. Herein, we describe a concept of genomics‐guided approach by performing genome mining and heterologous expression to uncover novel CDPS‐derived DKPs and functionally characterize novel tailoring enzymes embedded in the biosynthetic pathways. Recent works focused on the identification of the nucleobase‐related and dimeric DKPs are also presented. Genome mining combined with heterologous expression has been demonstrated to be an efficient way to identify novel 2,5‐diketopiperazine derivatives from actinobacteria. Meanwhile, their biosynthetic pathways and new enzymes embedded inside have been functionally characterized. It is expected that more biologically active diketopiperazines can be obtained by exploring the genetic potentials of microorganism in the future. |
| Author | Liu, Jing Li, Shu‐Ming |
| AuthorAffiliation | 2 Current address: Department of Natural Products in Organismic Interactions Max Planck Institute for Terrestrial Microbiology Karl-von-Frisch-Straße 10 35043 Marburg Germany 1 Institut für Pharmazeutische Biologie und Biotechnologie Fachbereich Pharmazie Philipps-Universität Marburg Robert-Koch-Straße 4 35037 Marburg Germany |
| AuthorAffiliation_xml | – name: 1 Institut für Pharmazeutische Biologie und Biotechnologie Fachbereich Pharmazie Philipps-Universität Marburg Robert-Koch-Straße 4 35037 Marburg Germany – name: 2 Current address: Department of Natural Products in Organismic Interactions Max Planck Institute for Terrestrial Microbiology Karl-von-Frisch-Straße 10 35043 Marburg Germany |
| Author_xml | – sequence: 1 givenname: Jing surname: Liu fullname: Liu, Jing organization: Max Planck Institute for Terrestrial Microbiology – sequence: 2 givenname: Shu‐Ming orcidid: 0000-0003-4583-2655 surname: Li fullname: Li, Shu‐Ming email: shuming.li@staff.uni-marburg.de organization: Philipps-Universität Marburg |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/36098493$$D View this record in MEDLINE/PubMed |
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| Keywords | nucleobase-containing DKPs heterologous expression 2,5-DKPs dimeric DKPs genome mining |
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| Snippet | Secondary metabolites derived from microorganism constitute an important part of natural products. Mining of the microbial genomes revealed a large number of... |
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| SubjectTerms | 2,5-DKPs Actinobacteria - genetics Actinobacteria - metabolism Bioinformatics Biological Products - metabolism Biosynthetic Pathways - genetics Computational Biology Concept Concepts Diketopiperazines dimeric DKPs Fermentation Gene clusters Gene expression genome mining Genomes Genomics heterologous expression Metabolites Microorganisms Multigene Family Natural products nucleobase-containing DKPs Secondary metabolites |
| Title | Genomics‐Guided Efficient Identification of 2,5‐Diketopiperazine Derivatives from Actinobacteria |
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