Abstract
Natural products and natural product-derived compounds have been widely used for pharmaceuticals for many years, and the search for new natural products that may have interesting activity is ongoing. Abyssomicins are natural product molecules that have antibiotic activity via inhibition of the folate synthesis pathway in microbiota. These compounds also appear to undergo a required [4 + 2] cycloaddition in their biosynthetic pathway. Here we report the structure of an flavin adenine dinucleotide-dependent reductase, AbsH3, from the biosynthetic gene cluster of novel abyssomicins found in Streptomyces sp. LC-6-2.
| Original language | English |
|---|---|
| Pages (from-to) | 132-137 |
| Number of pages | 6 |
| Journal | Proteins: Structure, Function and Bioinformatics |
| Volume | 89 |
| Issue number | 1 |
| DOIs |
|
| State | Published - Jan 2021 |
Bibliographical note
Publisher Copyright:© 2020 Wiley Periodicals LLC.
Funding
This work was supported by the Protein Structure Initiative project, Enzyme Discovery for Natural Product Biosynthesis (NATPRO) with NIH/NIGMS Grant number: U01GM098248, as well as NIH grants R01 CA217255 and R01 GM115261. This work was partially supported by a training fellowship for Jonathan Clinger from the Keck Center of the Gulf Coast Consortia, as part of the Houston Area Molecular Biophysics Program, National Institute of General Medical Sciences (NIGMS) T32GM008280. This research used resources of the Advanced Photon Source, a U.S. Department of Energy (DOE) Office of Science User Facility operated for the DOE Office of Science by Argonne National Laboratory under Contract No. DE-AC02-06CH11357. Use of the Lilly Research Laboratories Collaborative Access Team (LRL-CAT) beamline at Sector 31 of the Advanced Photon Source was provided by Eli Lilly Company, which operates the facility. This work was supported by the Protein Structure Initiative project, Enzyme Discovery for Natural Product Biosynthesis (NATPRO) with NIH/NIGMS Grant number: U01GM098248, as well as NIH grants R01 CA217255 and R01 GM115261. This work was partially supported by a training fellowship for Jonathan Clinger from the Keck Center of the Gulf Coast Consortia, as part of the Houston Area Molecular Biophysics Program, National Institute of General Medical Sciences (NIGMS) T32GM008280. This research used resources of the Advanced Photon Source, a U.S. Department of Energy (DOE) Office of Science User Facility operated for the DOE Office of Science by Argonne National Laboratory under Contract No. DE‐AC02‐06CH11357. Use of the Lilly Research Laboratories Collaborative Access Team (LRL‐CAT) beamline at Sector 31 of the Advanced Photon Source was provided by Eli Lilly Company, which operates the facility.
| Funders | Funder number |
|---|---|
| Enzyme Discovery for Natural Product Biosynthesis | |
| Keck Center of the Gulf Coast Consortia, as part of the Houston Area Molecular Biophysics Program | |
| Lilly Research Laboratories | |
| Protein Structure Initiative NatPro Project | |
| National Institutes of Health (NIH) | R01 GM115261 |
| Michigan State University-U.S. Department of Energy (MSU-DOE) Plant Research Laboratory | |
| National Childhood Cancer Registry – National Cancer Institute | R01CA217255 |
| National Institute of General Medical Sciences | U01GM098248, T32GM008280 |
| Eli Lilly and Company | |
| Office of Science Programs | |
| Argonne National Laboratory | DE‐AC02‐06CH11357 |
Keywords
- X-ray crystallography
- antibiotics
- ice rings
- natural product
- oxidoreductase
ASJC Scopus subject areas
- Structural Biology
- Biochemistry
- Molecular Biology