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 language | English |
|---|---|
| Pages (from-to) | 466-470 |
| Number of pages | 5 |
| Journal | ChemBioChem |
| Volume | 17 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - 15-03-2016 |
| Externally published | Yes |
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All Science Journal Classification (ASJC) codes
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Organic Chemistry
Cite this
}
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 journal › Article
TY - JOUR
T1 - Aliphatic Halogenase Enables Late-Stage C-H Functionalization
T2 - Selective Synthesis of a Brominated Fischerindole Alkaloid with Enhanced Antibacterial Activity
AU - Zhu, Qin
AU - Hillwig, Matthew L.
AU - Doi, Yohei
AU - Liu, Xinyu
PY - 2016/3/15
Y1 - 2016/3/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84959422901&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84959422901&partnerID=8YFLogxK
U2 - 10.1002/cbic.201500674
DO - 10.1002/cbic.201500674
M3 - Article
C2 - 26749394
AN - SCOPUS:84959422901
VL - 17
SP - 466
EP - 470
JO - ChemBioChem
JF - ChemBioChem
SN - 1439-4227
IS - 6
ER -