合成生物学 ›› 2021, Vol. 2 ›› Issue (5): 697-715.DOI: 10.12211/2096-8280.2021-012
杨谦1, 程伯涛1, 汤志军1, 刘文1,2
收稿日期:
2021-01-27
修回日期:
2021-04-05
出版日期:
2021-11-19
发布日期:
2021-11-19
通讯作者:
刘文
作者简介:
基金资助:
Qian YANG1, Botao CHENG1, Zhijun TANG1, Wen LIU1,2
Received:
2021-01-27
Revised:
2021-04-05
Online:
2021-11-19
Published:
2021-11-19
Contact:
Wen LIU
摘要:
天然产物一直以来都是药物先导化合物的重要来源。在药物发现领域,基因组数据常用来识别潜在的药物靶点或寻找先前被忽视的天然产物的生物合成基因簇。尽管基因组测序发现了微生物和植物中存在大量未开发的化学多样性,然而,仅仅利用传统的分离分析方法获取新的天然产物已经无法满足药物发展的需求。随着基因组时代的到来,数字化的基因组挖掘已经成为天然产物发现的重要组成部分。伴随着高通量测序方法的发展和DNA数据的丰富,各种基因组挖掘方法和工具被开发出来,以指导发现和表征这些天然产物。本文综述了近年来基因组挖掘的网络工具、数据库和方法,着重介绍次级代谢产物生物合成基因簇的挖掘手段,从经典的基因组挖掘到基于抗性基因挖掘、基于系统进化发育的挖掘,并对基因组挖掘在天然产物发现中的地位和前景进行了展望。
中图分类号:
杨谦, 程伯涛, 汤志军, 刘文. 基因组挖掘在天然产物发现中的应用和前景[J]. 合成生物学, 2021, 2(5): 697-715.
Qian YANG, Botao CHENG, Zhijun TANG, Wen LIU. Applications and prospects of genome mining in the discovery of natural products[J]. Synthetic Biology Journal, 2021, 2(5): 697-715.
数据库或web工具 | 网址(URL) | 参考文献 |
---|---|---|
天然产物数据库 | ||
Dictionary of Natural Products(DNP) | http://dnp.chemnetbase.com | [ |
The Natural Products Atlas | https://www.npatlas.org | [ |
PubMed | https://pubmed.ncbi.nlm.nih.gov/ | |
NPASS | http://bidd2.nus.edu.sg/NPASS | [ |
StreptomeDB | http://132.230.56.4/streptomedb2/ | [ |
MarinLit | http://pubs.rsc.org/marinlit/ | |
AntiBase | https://sciencesolutions.wiley.com | |
KNApSAcK | http://kanaya.naist.jp/KNApSAcK/ | [ |
Norine | https://bioinfo.lifl.fr/norine/ | [ |
MacrolactoneDB | https://macrolact.collaborationspharma.com/ | [ |
ChEBI | http://www.ebi.ac.uk/chebi/ | [ |
ChEMBl | https://www.ebi.ac.uk/chembl/ | [ |
ChemSpider | http://www.chemspider.com/ | [ |
COCONUT | https://doi.org/10.5281/zenod | [ |
生物合成基因簇数据库 | ||
ClusterMine360 | http://www.clustermine360.ca/ | [ |
DoBISCUIT | http://www.bio.nite.go.jp/pks/ | [ |
MIBiG | https://mibig.secondarymetabolites.org/ | [ |
IMG-ABC | https://img.jgi.doe.gov/cgi-bin/abc/main.cgi | [ |
antiSMASH Database | https://antismash.secondarymetabolites.org/ | [ |
ClustScan Database | http://csdb.bioserv.pbf.hr/csdb/ | [ |
BiG-FAM | https://bigfam.bioinformatics.nl/ | [ |
蛋白家族数据库 | ||
UniProtKB | https://www.uniprot.org/ | [ |
Pfam | http://pfam.xfam.org/ | [ |
InterPro | http://www.ebi.ac.uk/interpro/ | [ |
识别生物合成基因簇的网络工具 | ||
BLAST | https://blast.ncbi.nlm.nih.gov/Blast.cgi | [ |
HMMer | http://hmmer.org/ | [ |
ClustScan | http://bioserv.pbf.hr/cms/ | [ |
np.searcher | http://dna.sherman.lsi.umich.edu/ | [ |
SMURF | http://jcvi.org/smurf/index.php | [ |
antiSMASH | http://antismash.secondarymetabolites.org | [ |
ClusterFinder | https://github.com/petercim/ClusterFinder | [ |
RODEO | http://rodeo.scs.illinois.edu/ | [ |
表1 基因组挖掘的数据库及网络工具
Tab. 1 Database and web tools of genome mining
数据库或web工具 | 网址(URL) | 参考文献 |
---|---|---|
天然产物数据库 | ||
Dictionary of Natural Products(DNP) | http://dnp.chemnetbase.com | [ |
The Natural Products Atlas | https://www.npatlas.org | [ |
PubMed | https://pubmed.ncbi.nlm.nih.gov/ | |
NPASS | http://bidd2.nus.edu.sg/NPASS | [ |
StreptomeDB | http://132.230.56.4/streptomedb2/ | [ |
MarinLit | http://pubs.rsc.org/marinlit/ | |
AntiBase | https://sciencesolutions.wiley.com | |
KNApSAcK | http://kanaya.naist.jp/KNApSAcK/ | [ |
Norine | https://bioinfo.lifl.fr/norine/ | [ |
MacrolactoneDB | https://macrolact.collaborationspharma.com/ | [ |
ChEBI | http://www.ebi.ac.uk/chebi/ | [ |
ChEMBl | https://www.ebi.ac.uk/chembl/ | [ |
ChemSpider | http://www.chemspider.com/ | [ |
COCONUT | https://doi.org/10.5281/zenod | [ |
生物合成基因簇数据库 | ||
ClusterMine360 | http://www.clustermine360.ca/ | [ |
DoBISCUIT | http://www.bio.nite.go.jp/pks/ | [ |
MIBiG | https://mibig.secondarymetabolites.org/ | [ |
IMG-ABC | https://img.jgi.doe.gov/cgi-bin/abc/main.cgi | [ |
antiSMASH Database | https://antismash.secondarymetabolites.org/ | [ |
ClustScan Database | http://csdb.bioserv.pbf.hr/csdb/ | [ |
BiG-FAM | https://bigfam.bioinformatics.nl/ | [ |
蛋白家族数据库 | ||
UniProtKB | https://www.uniprot.org/ | [ |
Pfam | http://pfam.xfam.org/ | [ |
InterPro | http://www.ebi.ac.uk/interpro/ | [ |
识别生物合成基因簇的网络工具 | ||
BLAST | https://blast.ncbi.nlm.nih.gov/Blast.cgi | [ |
HMMer | http://hmmer.org/ | [ |
ClustScan | http://bioserv.pbf.hr/cms/ | [ |
np.searcher | http://dna.sherman.lsi.umich.edu/ | [ |
SMURF | http://jcvi.org/smurf/index.php | [ |
antiSMASH | http://antismash.secondarymetabolites.org | [ |
ClusterFinder | https://github.com/petercim/ClusterFinder | [ |
RODEO | http://rodeo.scs.illinois.edu/ | [ |
图7 从BCAA生物合成路径中关键的DHAD酶出发挖掘天然除草剂AA[102]
Fig. 7 Genome mining of a natural herbicide aspterric acid (AA) from the critical DHAD enzyme in the BCAA biosynthesis pathways
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