Synthetic Biology Advanced Natural Product Discovery
Abstract
:1. Introduction
2. The Design Stage for Natural Product Discovery
3. The Build Stage for Natural Product Discovery
4. The Test Stage for Natural Product Discovery
5. The Learning Stage for Natural Product Discovery
6. Conclusions and Future Perspectives
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Conflicts of Interest
References
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Name | Description | Web Address |
---|---|---|
Cluster mining tools | ||
antiSMASH | Web application to mine and analyze bacterial and fungal genome for secondary metabolite BGCs | https://antismash.secondarymetabolites.org (accessed on 5 July 2021) |
Mibig 2.0 | A robust community standard for annotation of metadata on BGCs and their molecular products | https://mibig.secondarymetabolites.org/ (accessed on 5 July 2021) |
ClusterCAD | A database and web-based toolkit to harness the potential of type I modular polyketide synthases for combinatorial biosynthesis | https://clustercad.jbei.org/ (accessed on 5 July 2021) |
PRISM 3 | Web for prediction of genetically encoded NRPs and PKs | http://magarveylab.ca/prism/ (accessed on 5 July 2021) |
RODEO | Algorithm developed to identify ribosomally synthesized and post-translationally modified peptide BGCs | http://www.ripprodeo.org (accessed on 7 July 2021) |
Bagel2 | Annotation of putative bacteriocins and antibiotics from genomic DNA | http://bagel2.molgenrug.nl/ (accessed on 7 July 2021) |
CLUSEAN | Identification of domains and prediction of specificities for PKS and NRPS genes | https://bitbucket.org/tilmweber/clusean (accessed on 7 July 2021) |
SBSPKS | Structural modeling of PKS modules and identification of key residues in the interfaces between modular PKS subunits | http://www.nii.ac.in/sbspks.html (accessed on 10 July 2021) |
SMURF | Annotation of PKS, NRPS, NRPS-PKS hybrid, indole alkoloid and terpene BGCs from fungal genomic DNA | http://jcvi.org/smurf/index.Php (accessed on 10 July 2021) |
2metDB | A tool offers the possibility to identify PKS and NRPS BGCs | http://secmetdb.sourceforge.net/ (accessed on 10 July 2021) |
ClusterFinder | A tool to detect putative BGCs in genomic and metagenomic data | https://github.com/petercim/ClusterFinder (accessed on 10 July 2021) |
eSNaPD | A tool to survey BGCs diversity in metagenomic DNA sequences | http://esnapd2.rockefeller.edu/ (accessed on 10 July 2021) |
EvoMining | Web for phylogenomics to identify BGCs | http://148.247.230.39/newevomining/new/evomining_web/index.html (accessed on 13 July 2021) |
MIDDAS-M | A tool that uses genome and transcriptome data to identify BGCs in fungal genomes | http://133.242.13.217/MIDDAS-M/ (accessed on 13 July 2021) |
MIPS-CG | Web application to identify BGCs with genome data | http://www.fung-metb.net/ (accessed on 13 July 2021) |
IMG-ABC | Database of experimentally verified and predicted BGCs across 40,000 isolated microbial genomes | https://img.jgi.doe.gov/abc/ (accessed on 13 July 2021) |
NaPDoS | Web for offering analysis of PKS/NRPS | http://napdos.ucsd.edu/ (accessed on 15 July 2021) |
PKS/NRPS analytic tools | ||
NP.searcher | Web application to identify PKS and NRPS BGCs | http://dna.sherman.lsi.umich.edu (accessed on 15 July 2021) |
ClustScan | Web accessible database for PKS/NRPS BGCs | http://csdb.bioserv.pbf.hr/csdb/ClustScanWeb.html (accessed on 19 July 2021) |
GNP | Web application to identify BGCs (mainly PKS/NRPS) | http://magarveylab.ca/gnp/ (accessed on 19 July 2021) |
NRPS-PKS | Web application to identify PKS BGCs | http://www.nii.res.in/nrps-pks.html (accessed on 19 July 2021) |
Specificity predictors for NRPS or PKS | ||
NRPS/PKS substrate predictor | Web for predicting A-domain or AT-domain | http://www.cmbi.ru.nl/NRPS-PKS-substrate-predictor/ (accessed on 21 July 2021) |
LSI-based A-domain function predictor | Web for predicting A-domain | http://bioserv7.bioinfo.pbf.hr/LSIpredictor/AdomainPrediction.jsp (accessed on 21 July 2021) |
NRPSsp | Web for predicting A-domain | http://www.nrpssp.com/ (accessed on 21 July 2021) |
ASMPKS | Web for identification of PKS genes from genomic DNA | http://gate.smallsoft.co.kr:8008/pks/ (accessed on 21 July 2021) |
PKS/NRPS Web Server/Predictive Blast Server | Web for predicting A-domain specificities | http://nrps.igs.umaryland.edu/nrps/ (accessed on 21 July 2021) |
Compounds databases | ||
ChEBI | A database and ontology of chemical compounds focusing on small molecules | https://www.ebi.ac.uk/chebi/ (accessed on 21 July 2021) |
ChEMBL | A database providing information on bioactive molecules with drug-like properties | https://www.ebi.ac.uk/chembl/ (accessed on 21 July 2021) |
ChemSpider | A database providing information on structures and properties of over 35 million structures | http://www.chemspider.com/ (accessed on 21 July 2021) |
KNApSAcK database | A database on compound information of more than 50,000 natural products of plants and microorganisms | http://kanaya.aist-nara.ac.jp/KNApSAcK/ (accessed on 21 July 2021) |
PubChem | A database contains synthetic compounds as well as natural products | http://pubchem.ncbi.nlm.nih.gov/ (accessed on 21 July 2021) |
Metabolomics tools | ||
GNPS | Web for analyzing mass spectrometry (MS)/MS data | http://gnps.ucsd.edu/ (accessed on 21 July 2021) |
GNP/iSNAP | Web application to automatically identify metabolites in MS/MS data | http://magarveylab.ca/gnp/ (accessed on 21 July 2021) |
NRPquest | Web for correlating NRP data with gene clusters | http://cyclo.ucsd.edu (accessed on 21 July 2021) |
Pep2Path | Web for correlating peptide sequence tags with NRP and post-translationally modified peptide BGCs | http://pep2path.sourceforge.net (accessed on 21 July 2021) |
Category | DNA Assembly | Description | Reference |
---|---|---|---|
Restriction enzyme-based (in vitro) | Golden Gate assembly | A method that can assemble multiple DNA fragments using type IIs restriction enzymes | [34] |
Start-Stop assembly | A method that can assemble 60 DNA fragments by type IIs restriction enzymes | [35] | |
Homology-based (in vitro) | One-step sequence- and ligation-independent cloning (SLIC) | A method based on 3′-to-5′ exonuclease activity of T4 DNA polymerase | [36] |
Gibson assembly | A method by T5 exonuclease, Taq DNA ligase and Pfu DNA polymerase | [37] | |
T5 exonuclease DNA assembly (TEDA) | A method that requires only T5 exonuclease for assembling multiple DNA fragments | [38] | |
Ligase cycling reaction (LCR) assembly | A method that can assemble 20 DNA fragments in one step by introducing single-stranded bridging oligos between two neighboring DNA fragments | [39] | |
Homology-based (in vivo) | Transformation-associated recombination (TAR) | A method depending on the highly efficient homologous recombination system of S. cerevisiae | [40] |
Linear-linear homologous recombination (LLHR) | Suitable for cloning small- and midBGCs but require highly specialized capturing vectors and multi-rounds selection. | [41] | |
Exonuclease combined with RecET recombination (ExoCET) | A method using short recombination homologous arms. | [42] | |
CRISPR (in vivo) | Cas9-assisted targeting of chromosome segments (CATCH) | A method that can capture 100-kb DNA genomic sequences basing on Cas9 and Gibson assembly | [43] |
Programmable genome engineering | A method that can rearrange 1.55-Mb genome sequences by combining Cas9 and lambda-red recombination | [44] | |
Genome editing tools | |||
Gene regulation | Clustered regularly interspaced short palindromic repeats interference (CRISPRi) | The transcription of a gene is repressed by guide RNA and inactive Cas protein | [45] |
CRISPR-AID | A trifunctional system that can simultaneously achieve gene deletion, transcriptional activation and repression | [46] | |
Gene deletion | Multiplex automated genome engineering (MAGE) | Simultaneous editing of multiple genes by prototype devices that automate the MAGE technology | [31] |
Transcription activator-like effector nucleases (TALENs) | Simultaneous editing of multiple genes using TALENs with high portability | [47] | |
Zinc finger nucleases (ZFNs) | Allows targeted genome editing but requires re-engineering for every new target site | [48] | |
gRNA-tRNA array for CRISPR-Cas9 (GTR-CRISPR) | Simultaneous disruption of 8 genes with high efficiency | [49] | |
Gene integration | Recombinase-assisted genome engineering (RAGE) | Multiplexed integration of large-size DNA constructs | [50] |
Delta integration CRISPR-Cas (Di-CRISPR) | High-efficiency, multicopy, markerless integrations of large biochemical pathways | [51] | |
Single-nucleotide conversion | GTR 2.0 | Multiplexed single-nucleotide conversions | [52] |
CRISPR-Cas9- and homology-directed-repair-assisted genome-scale engineering method (CHAnGE) | Rapidly output tens of thousands of specific genetic variants in yeast | [53] |
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Wang, J.; Nielsen, J.; Liu, Z. Synthetic Biology Advanced Natural Product Discovery. Metabolites 2021, 11, 785. https://0-doi-org.brum.beds.ac.uk/10.3390/metabo11110785
Wang J, Nielsen J, Liu Z. Synthetic Biology Advanced Natural Product Discovery. Metabolites. 2021; 11(11):785. https://0-doi-org.brum.beds.ac.uk/10.3390/metabo11110785
Chicago/Turabian StyleWang, Junyang, Jens Nielsen, and Zihe Liu. 2021. "Synthetic Biology Advanced Natural Product Discovery" Metabolites 11, no. 11: 785. https://0-doi-org.brum.beds.ac.uk/10.3390/metabo11110785