Aliphatic Halogenase Enables Late-Stage C-H Functionalization: Selective Synthesis of a Brominated Fischerindole Alkaloid with Enhanced Antibacterial Activity

Qin Zhu, Matthew L. Hillwig, Yohei Doi, Xinyu Liu

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

The anion promiscuity of a newly discovered standalone aliphatic halogenase WelO5 was probed and enabled the selective synthesis of 13R-bromo-12-epi-fischerindole U via late-stage enzymatic functionalization of an unactivated sp3 C-H bond. Pre-saturating the WelO5 active site with a non-native bromide anion was found to be critical to the highly selective in vitro transfer of bromine, instead of chlorine, to the target carbon center and also allowed the relative binding affinity of bromide and chloride towards the WelO5 enzyme to be assessed. This study further revealed the critical importance of halogen substitution on modulating the antibiotic activity of fischerindole alkaloids and highlights the promise of WelO5-type aliphatic halogenases as enzymatic tools to fine-tune the bioactivity of complex natural products.

Original languageEnglish
Pages (from-to)466-470
Number of pages5
JournalChemBioChem
Volume17
Issue number6
DOIs
Publication statusPublished - 15-03-2016
Externally publishedYes

Fingerprint

Bromides
Alkaloids
Anions
Bromine
Halogens
Chlorine
Bioactivity
Biological Products
Chlorides
Catalytic Domain
Substitution reactions
Carbon
Anti-Bacterial Agents
Enzymes
fischerindole
In Vitro Techniques

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Organic Chemistry

Cite this

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Aliphatic Halogenase Enables Late-Stage C-H Functionalization : Selective Synthesis of a Brominated Fischerindole Alkaloid with Enhanced Antibacterial Activity. / Zhu, Qin; Hillwig, Matthew L.; Doi, Yohei; Liu, Xinyu.

In: ChemBioChem, Vol. 17, No. 6, 15.03.2016, p. 466-470.

Research output: Contribution to journalArticle

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