Reassembly of the Biosynthetic Gene Cluster Enables High Epothilone Yield in Engineered

Bacterial Proteins / genetics Coenzyme A Ligases / genetics Comamonadaceae / chemistry Epothilones / biosynthesis Metabolic Engineering / methods Multigene Family Plasmids / genetics Polyketide Synthases / genetics Polyketides / chemistry Promoter Regions, Genetic Racemases and Epimerases / genetics Sorangium / genetics
NRP/PK Schlegelella brevitalea biosynthetic gene cluster epothilone metabolic engineering

Journal

ACS synthetic biology
ISSN: 2161-5063
Titre abrégé: ACS Synth Biol
Pays: United States
ID NLM: 101575075

Informations de publication

Date de publication:
21 08 2020
Historique:
pubmed: 1 7 2020
medline: 28 5 2021
entrez: 1 7 2020
Statut: ppublish

Résumé

Epothilones, as a new class of microtubule-stabilizing anticancer drugs, exhibit strong bioactivity against taxane-resistant cells and show clinical activity for the treatment of advanced breast cancer. Additionally, they also show great potential for a central nervous system injury and Alzheimer's disease. However, due to the long fermentation period of the original producer and challenges of genetic engineering of nonribosomal peptide/polyketide (NRP/PK) megasynthase genes, the application of epothilones is severely limited. Here, we addressed these problems by reassembling a novel 56-kb epothilone biosynthetic gene cluster, optimizing the promoter of each gene based on RNA-seq profiling, and completing precursor synthetic pathways in engineered

Identifiants

DOI: 10.1021/acssynbio.0c00100 PMID: 32603592
pubmed: 32603592
doi: 10.1021/acssynbio.0c00100
doi:

Substances chimiques

Bacterial Proteins 0
Epothilones 0
Polyketides 0
Polyketide Synthases 79956-01-7
Racemases and Epimerases EC 5.1.-
Coenzyme A Ligases EC 6.2.1.-
malonyl-CoA synthetase EC 6.2.1.-

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2009-2022

Auteurs

Yucong Yu (Y)

Collaborative Innovation Center for Genetics and Development, State Key Laboratory of Genetic Engineering, Department of Microbiology, School of Life Sciences, Fudan University, Shanghai, 200438, People's Republic of China.
ORCID: 0000-0002-4846-2461

Huimin Wang (H)

Collaborative Innovation Center for Genetics and Development, State Key Laboratory of Genetic Engineering, Department of Microbiology, School of Life Sciences, Fudan University, Shanghai, 200438, People's Republic of China.
ORCID: 0000-0002-3955-3687

Biao Tang (B)

Collaborative Innovation Center for Genetics and Development, State Key Laboratory of Genetic Engineering, Department of Microbiology, School of Life Sciences, Fudan University, Shanghai, 200438, People's Republic of China.
Institute of Quality and Standard for Agro-products, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, People's Republic of China.

Junheng Liang (J)

Collaborative Innovation Center for Genetics and Development, State Key Laboratory of Genetic Engineering, Department of Microbiology, School of Life Sciences, Fudan University, Shanghai, 200438, People's Republic of China.

Lin Zhang (L)

Collaborative Innovation Center for Genetics and Development, State Key Laboratory of Genetic Engineering, Department of Microbiology, School of Life Sciences, Fudan University, Shanghai, 200438, People's Republic of China.
ORCID: 0000-0001-5431-5006

Hongkuan Wang (H)

State Key Laboratory of Genetic Engineering and Ministry of Education Key Laboratory of Biodiversity Sciences and Ecological Engineering, Institute of Plant Biology, School of Life Sciences, Fudan University, Shanghai 200438, People's Republic of China.

Xiaoying Bian (X)

Shandong University-Helmholtz Institute of Biotechnology, State Key Laboratory of Microbial Technology, School of Life Sciences, Shandong University, Qingdao, Shandong 266237, People's Republic of China.
ORCID: 0000-0002-1356-3211

Yue-Zhong Li (YZ)

Shandong University-Helmholtz Institute of Biotechnology, State Key Laboratory of Microbial Technology, School of Life Sciences, Shandong University, Qingdao, Shandong 266237, People's Republic of China.
ORCID: 0000-0001-8336-6638

Youming Zhang (Y)

Shandong University-Helmholtz Institute of Biotechnology, State Key Laboratory of Microbial Technology, School of Life Sciences, Shandong University, Qingdao, Shandong 266237, People's Republic of China.

Guo-Ping Zhao (GP)

Collaborative Innovation Center for Genetics and Development, State Key Laboratory of Genetic Engineering, Department of Microbiology, School of Life Sciences, Fudan University, Shanghai, 200438, People's Republic of China.
CAS Key Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200032, People's Republic of China.

Xiaoming Ding (X)

Collaborative Innovation Center for Genetics and Development, State Key Laboratory of Genetic Engineering, Department of Microbiology, School of Life Sciences, Fudan University, Shanghai, 200438, People's Republic of China.

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Classifications MeSH

questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines bactériennes › Reassembly of the Biosynthetic Gene Cluster...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Ligases › Carbon-sulfur ligases › Coenzyme A ligases › Reassembly of the Biosynthetic Gene Cluster...
questionsmedicales.fr › Bactéries › Proteobacteria › Betaproteobacteria › Burkholderiales › Comamonadaceae › Reassembly of the Biosynthetic Gene Cluster...
questionsmedicales.fr › Composés chimiques organiques › Lactones › Épothilones › Reassembly of the Biosynthetic Gene Cluster...
questionsmedicales.fr › Technologie, industrie et agriculture › Ingénierie › Bioingénierie › Ingénierie cellulaire › Génie métabolique › Reassembly of the Biosynthetic Gene Cluster...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Génome › Composants de génome › Gènes › Famille multigénique › Reassembly of the Biosynthetic Gene Cluster...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Plasmides › Reassembly of the Biosynthetic Gene Cluster...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Complexes multienzymatiques › Polyketide synthases › Reassembly of the Biosynthetic Gene Cluster...
questionsmedicales.fr › Composés polycycliques › Composés macrocycliques › Polycétides › Reassembly of the Biosynthetic Gene Cluster...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Génome › Composants de génome › Gènes › Composants de gène › Éléments de régulation transcriptionnelle › Régions promotrices (génétique) › Reassembly of the Biosynthetic Gene Cluster...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Isomerases › Racémases et épimérases › Reassembly of the Biosynthetic Gene Cluster...
questionsmedicales.fr › Bactéries › Proteobacteria › Deltaproteobacteria › Myxococcales › Sorangium (genre) › Reassembly of the Biosynthetic Gene Cluster...