Evidence map›Paper›PMID 35817967›Full record

ArticleNature chemical biology2022

Engineering site-selective incorporation of fluorine into polyketides.

Sasilada Sirirungruang, Omer Ad, Thomas M Privalsky, Swetha Ramesh, Joel L Sax, Hongjun Dong, Edward E K Baidoo, Bashar Amer, Chaitan Khosla, Michelle C Y Chang

Abstract read
In one paragraph

Article in Nature chemical biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing 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

31 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Harnessing Photoenzymatic Systems for Intermolecular C-H Fluorination.Angewandte Chemie (International ed. in English) · 2026
    Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Review
  12. Article
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  14. Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Biocatalytic enantioselective C(spNature synthesis · 2024
    Article
  20. 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

10 authors.

Sasilada SirirungruangDepartment of Molecular and Cell Biology, University of California, Berkeley, CA, USA.ORCID http://orcid.org/0000-0002-2624-5124
Omer AdDepartment of Chemistry, University of California, Berkeley, CA, USA.
Thomas M PrivalskyDepartment of Chemistry, Stanford University, Stanford, CA, USA.
Swetha RameshDepartment of Molecular and Cell Biology, University of California, Berkeley, CA, USA.ORCID http://orcid.org/0000-0001-7833-165X
Joel L SaxDepartment of Molecular and Cell Biology, University of California, Berkeley, CA, USA.
Hongjun DongDepartment of Chemistry, University of California, Berkeley, CA, USA.
Edward E K BaidooJoint Bioenergy Institute, Lawrence Berkeley National Laboratory, Emeryville, CA, USA.
Bashar AmerJoint Bioenergy Institute, Lawrence Berkeley National Laboratory, Emeryville, CA, USA.
Chaitan KhoslaDepartment of Chemistry, Stanford University, Stanford, CA, USA.
Michelle C Y ChangDepartment of Molecular and Cell Biology, University of California, Berkeley, CA, USA. mcchang@berkeley.edu.ORCID http://orcid.org/0000-0003-3747-7630

Funding

Univ of Calif Berkeley Chemistry-Biology Interface ProgramT32GM066698 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI CHANG, CHRISTOPHER J., FRANCIS, MATTHEW B · 2004 to 2023
$7.5M
Mechanisms and Evolution of Assembly-Line Polyketide SynthasesR35GM141799 · NIGMS · STANFORD UNIVERSITY · PI CHAITAN KHOSLA · 2021 to 2026
$2.5M
Synthetic Biology Approaches to New Fluorinated PharmaceuticalsR01GM123181 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI CHANG, MICHELLE C · 2017 to 2020
$1.3M
Acquisition of a Cryoprobe and Related Accessories for a 600 MHz NMR Spectrometer to Support Health Research Activities at the University of California, BerkeleyS10OD024998 · OD · UNIVERSITY OF CALIFORNIA BERKELEY · PI HARTWIG, JOHN F · 2018 to 2018
$265k
NIGMS NIH HHS R01 GM123181NIGMS NIH HHS R35 GM141799NIGMS NIH HHS T32 GM066698NIH HHS S10 OD024998
6 · The paper itself

Abstract

Although natural products and synthetic small molecules both serve important medicinal functions, their structures and chemical properties are relatively distinct. To expand the molecular diversity available for drug discovery, one strategy is to blend the effective attributes of synthetic and natural molecules. A key feature found in synthetic compounds that is rare in nature is the use of fluorine to tune drug behavior. We now report a method to site-selectively incorporate fluorine into complex structures to produce regioselectively fluorinated full-length polyketides. We engineered a fluorine-selective trans-acyltransferase to produce site-selectively fluorinated erythromycin precursors in vitro. We further demonstrated that these analogs could be produced in vivo in Escherichia coli on engineering of the fluorinated extender unit pool. By using engineered microbes, elaborate fluorinated compounds can be produced by fermentation, offering the potential for expanding the identification and development of bioactive fluorinated small molecules.

Indexed as

Biological ProductsPolyketidesAcyltransferasesEscherichia coliFluorineAcyltransferasesBiological ProductsFluorinePolyketides

Identifiers

PMID35817967
PMCPMC10030150

What OpenQuestion holds

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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.