PMID- 34257844
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210715
IS  - 2001-0370 (Print)
IS  - 2001-0370 (Electronic)
IS  - 2001-0370 (Linking)
VI  - 19
DP  - 2021
TI  - Computational biotechnology guides elucidation of the biosynthesis of the plant 
      anticancer drug camptothecin.
PG  - 3659-3663
LID - 10.1016/j.csbj.2021.06.028 [doi]
AB  - Camptothecin is a clinically important monoterpene indole alkaloid (MIAs) used 
      for treating various cancers. Currently, the production of this biopharmaceutical 
      hinges on its extraction from camptothecin-producing plants, leading to high 
      market prices and supply bottlenecks. While synthetic biology combined with 
      metabolic approaches could represent an attractive alternative approach to 
      manufacturing, it requires firstly a complete biosynthetic pathway elucidation, 
      which is, unfortunately, severely missing in species naturally accumulating 
      camptothecin. This knowledge gap can be attributed to the lack of high-quality 
      genomic resources of medicinal plant species. In such a perspective, Yamazaki and 
      colleagues produced the first described and experimentally validated 
      chromosome-level plant genome assembly of Ophiorrhiza pumila, a prominent source 
      plant of camptothecin for the pharmaceutical industry. More specifically, they 
      have developed a method incorporating Illumina reads, PacBio single-molecule 
      reads, optical mapping and Hi-C sequencing, followed by the experimental 
      validation of contig orientation within scaffolds, using fluorescence in situ 
      hybridization (FISH) analysis. This relevant strategy resulted in the most 
      contiguous and complete de novo plant reference genome described to date, which 
      can streamline the sequencing of new plant genomes. Further mining approaches, 
      including integrative omics analysis, phylogenetics, gene cluster evaluation and 
      comparative genomics were successfully used to puzzle out the evolutionary 
      origins of MIA metabolism and revealed a short-list of high confidence MIA 
      biosynthetic genes for functional validation.
CI  - (c) 2021 The Authors. Published by Elsevier B.V. on behalf of Research Network of 
      Computational and Structural Biotechnology.
FAU - Stander, Emily Amor
AU  - Stander EA
AD  - Universite de Tours, EA2106 "Biomolecules et Biotechnologies Vegetales", Tours, 
      France.
FAU - Duge de Bernonville, Thomas
AU  - Duge de Bernonville T
AD  - Universite de Tours, EA2106 "Biomolecules et Biotechnologies Vegetales", Tours, 
      France.
FAU - Papon, Nicolas
AU  - Papon N
AD  - Univ Angers, Univ Brest, GEIHP, SFR ICAT, Angers, France.
FAU - Courdavault, Vincent
AU  - Courdavault V
AD  - Universite de Tours, EA2106 "Biomolecules et Biotechnologies Vegetales", Tours, 
      France.
LA  - eng
PT  - Journal Article
DEP - 20210622
PL  - Netherlands
TA  - Comput Struct Biotechnol J
JT  - Computational and structural biotechnology journal
JID - 101585369
PMC - PMC8254074
OTO - NOTNLM
OT  - Biosynthetic pathway
OT  - Genome mining
OT  - Medicinal plants
OT  - Next-generation sequencing
OT  - Pharmaceuticals
OT  - Synthetic biology
COIS- The authors declare that they have no known competing financial interests or 
      personal relationships that could have appeared to influence the work reported in 
      this paper.
EDAT- 2021/07/15 06:00
MHDA- 2021/07/15 06:01
PMCR- 2021/06/22
CRDT- 2021/07/14 07:04
PHST- 2021/03/11 00:00 [received]
PHST- 2021/06/18 00:00 [revised]
PHST- 2021/06/18 00:00 [accepted]
PHST- 2021/07/14 07:04 [entrez]
PHST- 2021/07/15 06:00 [pubmed]
PHST- 2021/07/15 06:01 [medline]
PHST- 2021/06/22 00:00 [pmc-release]
AID - S2001-0370(21)00266-X [pii]
AID - 10.1016/j.csbj.2021.06.028 [doi]
PST - epublish
SO  - Comput Struct Biotechnol J. 2021 Jun 22;19:3659-3663. doi: 
      10.1016/j.csbj.2021.06.028. eCollection 2021.