Evidence map›Paper›PMID 30767524›Full record

ArticleJournal of the American Chemical Society2019

Rational Reprogramming of O-Methylation Regioselectivity for Combinatorial Biosynthetic Tailoring of Benzenediol Lactone Scaffolds.

Xiaojing Wang, Chen Wang, Lixin Duan, Liwen Zhang, Hang Liu, Ya-Ming Xu, Qingpei Liu, Tonglin Mao, Wei Zhang, Ming Chen and 4 more

Abstract read
In one paragraph

Article in Journal of the American Chemical Society, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

21 citing papers in PubMed.

  1. A novel C5-Horticulture research · 2026
    Article
  2. Article
  3. Review
  4. Article
  5. The divergence of DHN-derived melanin pathways in Metarhizium robertsii.World journal of microbiology & biotechnology · 2024
    Article
  6. Review
  7. Biosynthesis of Cytosporones in Leotiomycetous Filamentous Fungi.Journal of the American Chemical Society · 2024
    Article
  8. Review
  9. Article
  10. Methyltransferases: Functions and Applications.Chembiochem : a European journal of chemical biology · 2022
    Review
  11. Functional Characterization of a Regiospecific Sugar-Applied and environmental microbiology · 2022
    Article
  12. Metabolic engineering communications · 2022
    Article
  13. Article
  14. Article
  15. Enzymatic Late-Stage Modifications: Better Late Than Never.Angewandte Chemie (International ed. in English) · 2021
    Review
  16. Enzymkatalysierte späte Modifizierungen: Besser spät als nie.Angewandte Chemie (Weinheim an der Bergstrasse, Germany) · 2021
    Review
  17. Article
  18. Article
  19. Article
  20. Synthetic biology enabling access to designer polyketides.Current opinion in chemical biology · 2020
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Xiaojing WangBiotechnology Research Institute , Chinese Academy of Agricultural Sciences , 12 Zhongguancun South Street , Beijing 100081 , P.R. China.
Chen WangBiotechnology Research Institute , Chinese Academy of Agricultural Sciences , 12 Zhongguancun South Street , Beijing 100081 , P.R. China.ORCID 0000-0001-8639-647X
Lixin DuanSouthwest Center for Natural Products Research , University of Arizona , 250 East Valencia Road , Tucson , Arizona 85706 , United States.
Liwen ZhangBiotechnology Research Institute , Chinese Academy of Agricultural Sciences , 12 Zhongguancun South Street , Beijing 100081 , P.R. China.
Hang LiuBiotechnology Research Institute , Chinese Academy of Agricultural Sciences , 12 Zhongguancun South Street , Beijing 100081 , P.R. China.
Ya-Ming XuSouthwest Center for Natural Products Research , University of Arizona , 250 East Valencia Road , Tucson , Arizona 85706 , United States.
Qingpei LiuSouthwest Center for Natural Products Research , University of Arizona , 250 East Valencia Road , Tucson , Arizona 85706 , United States.
Tonglin MaoState Key Laboratory of Plant Physiology and Biochemistry, Department of Plant Sciences, College of Biological Sciences , China Agricultural University , Beijing 100193 , P.R. China.
Wei ZhangBiotechnology Research Institute , Chinese Academy of Agricultural Sciences , 12 Zhongguancun South Street , Beijing 100081 , P.R. China.
Ming ChenBiotechnology Research Institute , Chinese Academy of Agricultural Sciences , 12 Zhongguancun South Street , Beijing 100081 , P.R. China.
Min LinBiotechnology Research Institute , Chinese Academy of Agricultural Sciences , 12 Zhongguancun South Street , Beijing 100081 , P.R. China.
A A Leslie GunatilakaSouthwest Center for Natural Products Research , University of Arizona , 250 East Valencia Road , Tucson , Arizona 85706 , United States.ORCID 0000-0001-9663-3600
Yuquan XuBiotechnology Research Institute , Chinese Academy of Agricultural Sciences , 12 Zhongguancun South Street , Beijing 100081 , P.R. China.
István MolnárSouthwest Center for Natural Products Research , University of Arizona , 250 East Valencia Road , Tucson , Arizona 85706 , United States.ORCID 0000-0002-3627-0454

Funding

Combinatorial biosynthesis of fungal benzenediol lactone polyketidesR01GM114418 · NIGMS · UNIVERSITY OF ARIZONA · PI MOLNAR, ISTVAN · 2016 to 2019
$1.4M
NIGMS NIH HHS R01 GM114418
6 · The paper itself

Abstract

O-Methylation modulates the pharmacokinetic and pharmacodynamic (PK/PD) properties of small-molecule natural products, affecting their bioavailability, stability, and binding to targets. Diversity-oriented combinatorial biosynthesis of new chemical entities for drug discovery and optimization of known bioactive scaffolds during drug development both demand efficient O-methyltransferase (OMT) biocatalysts with considerable substrate promiscuity and tunable regioselectivity that can be deployed in a scalable and sustainable manner. Here we demonstrate efficient total biosynthetic and biocatalytic platforms that use a pair of fungal OMTs with orthogonal regiospecificity to produce unnatural O-methylated benzenediol lactone polyketides. We show that rational, structure-guided active-site cavity engineering can reprogram the regioselectivity of these enzymes. We also characterize the interplay of engineered regioselectivity with substrate plasticity. These findings will guide combinatorial biosynthetic tailoring of unnatural products toward the generation of diverse chemical matter for drug discovery and the PK/PD optimization of bioactive scaffolds for drug development.

Indexed as

Amino Acid SubstitutionAscomycotaCatalytic DomainHumansKineticsLactonesMethylationMethyltransferasesMolecular Docking SimulationPolyketidesProtein BindingProtein EngineeringSubstrate SpecificityZearalenoneZeranoldesmethyl-lasiodiplodinLactonesMethyltransferasesPolyketidesZearalenoneZeranol

Identifiers

PMID30767524
PMCPMC6416077

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.