Aliphatic Halogenase Enables Late‐Stage C−H Functionalization: Selective Synthesis of a Brominated Fischerindole Alkaloid with Enhanced Antibacterial Activity
The anion promiscuity of a newly discovered standalone aliphatic halogenase WelO5 was probed and enabled the selective synthesis of 13 R ‐bromo‐12‐ epi ‐fischerindole U via late‐stage enzymatic functionalization of an unactivated sp 3 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. Bromine dominates ! The promiscuous aliphatic halogenase WelO5 selectively brominated 12‐ epi ‐fischerindole U through late‐stage enzymatic functionalization of an unactivated sp 3 C−H bond, which showed eight times higher antibacterial activity against the human pathogen Staphylococcus aureus . This approach highlights the promise of enzyme‐mediated late‐stage aliphatic halogenation in tuning the potency of antibiotics..
| Medienart: |
Artikel |
|---|
| Erscheinungsjahr: |
2016 |
|---|---|
| Erschienen: |
2016 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:17 |
|---|---|
| Enthalten in: |
ChemBioChem - 17(2016), 6, Seite 466-470 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Zhu, Qin [VerfasserIn] |
|---|
| Links: |
Volltext |
|---|
| BKL: | |
|---|---|
| Themen: |
Alkaloid biogenesis |
| RVK: |
|---|
| doi: |
10.1002/cbic.201500674 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
OLC1973387662 |
|---|
| LEADER | 01000caa a2200265 4500 | ||
|---|---|---|---|
| 001 | OLC1973387662 | ||
| 003 | DE-627 | ||
| 005 | 20230714184543.0 | ||
| 007 | tu | ||
| 008 | 160427s2016 xx ||||| 00| ||eng c | ||
| 024 | 7 | |a 10.1002/cbic.201500674 |2 doi | |
| 028 | 5 | 2 | |a PQ20160430 |
| 035 | |a (DE-627)OLC1973387662 | ||
| 035 | |a (DE-599)GBVOLC1973387662 | ||
| 035 | |a (PRQ)p1614-d3f5341bc28cc73e8e1f9667eb6011cbdd497e4c2566753d1dd30ecc6d2e81a33 | ||
| 035 | |a (KEY)0431463820160000017000600466aliphatichalogenaseenableslatestagechfunctionaliza | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 082 | 0 | 4 | |a 32 |a 30 |a 570 |a 580 |a 590 |q DE-101 |
| 082 | 0 | 4 | |a 570 |q AVZ |
| 084 | |a BIODIV |2 fid | ||
| 084 | |a VA 2918 |q AVZ |2 rvk | ||
| 084 | |a 35.70 |2 bkl | ||
| 084 | |a 42.13 |2 bkl | ||
| 100 | 1 | |a Zhu, Qin |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Aliphatic Halogenase Enables Late‐Stage C−H Functionalization: Selective Synthesis of a Brominated Fischerindole Alkaloid with Enhanced Antibacterial Activity |
| 264 | 1 | |c 2016 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ohne Hilfsmittel zu benutzen |b n |2 rdamedia | ||
| 338 | |a Band |b nc |2 rdacarrier | ||
| 520 | |a The anion promiscuity of a newly discovered standalone aliphatic halogenase WelO5 was probed and enabled the selective synthesis of 13 R ‐bromo‐12‐ epi ‐fischerindole U via late‐stage enzymatic functionalization of an unactivated sp 3 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. Bromine dominates ! The promiscuous aliphatic halogenase WelO5 selectively brominated 12‐ epi ‐fischerindole U through late‐stage enzymatic functionalization of an unactivated sp 3 C−H bond, which showed eight times higher antibacterial activity against the human pathogen Staphylococcus aureus . This approach highlights the promise of enzyme‐mediated late‐stage aliphatic halogenation in tuning the potency of antibiotics. | ||
| 540 | |a Nutzungsrecht: © 2016 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim | ||
| 540 | |a © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. | ||
| 650 | 4 | |a antibiotics | |
| 650 | 4 | |a C−H activation | |
| 650 | 4 | |a non-heme iron enzymes | |
| 650 | 4 | |a halogenases | |
| 650 | 4 | |a alkaloid biogenesis | |
| 700 | 1 | |a Hillwig, Matthew L |4 oth | |
| 700 | 1 | |a Doi, Yohei |4 oth | |
| 700 | 1 | |a Liu, Xinyu |4 oth | |
| 773 | 0 | 8 | |i Enthalten in |t ChemBioChem |d Weinheim : Wiley-VCH Verl., 2000 |g 17(2016), 6, Seite 466-470 |w (DE-627)316515531 |w (DE-600)2019276-9 |w (DE-576)090103181 |x 1439-4227 |7 nnns |
| 773 | 1 | 8 | |g volume:17 |g year:2016 |g number:6 |g pages:466-470 |
| 856 | 4 | 1 | |u http://dx.doi.org/10.1002/cbic.201500674 |3 Volltext |
| 856 | 4 | 2 | |u http://onlinelibrary.wiley.com/doi/10.1002/cbic.201500674/abstract |
| 856 | 4 | 2 | |u http://www.ncbi.nlm.nih.gov/pubmed/26749394 |
| 856 | 4 | 2 | |u http://search.proquest.com/docview/1774536402 |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a SYSFLAG_A | ||
| 912 | |a GBV_OLC | ||
| 912 | |a FID-BIODIV | ||
| 912 | |a SSG-OLC-PHA | ||
| 912 | |a SSG-OLC-DE-84 | ||
| 936 | r | v | |a VA 2918 |
| 936 | b | k | |a 35.70 |q AVZ |
| 936 | b | k | |a 42.13 |q AVZ |
| 951 | |a AR | ||
| 952 | |d 17 |j 2016 |e 6 |h 466-470 | ||