1. Biochemistry and Chemical Biology
Download icon

Biochemical basis for the regulation of biosynthesis of antiparasitics by bacterial hormones

  1. Iti Kapoor
  2. Philip Olivares
  3. Satish K Nair  Is a corresponding author
  1. University of Illinois at Urbana-Champaign, United States
Research Article
  • Cited 0
  • Views 851
  • Annotations
Cite this article as: eLife 2020;9:e57824 doi: 10.7554/eLife.57824

Abstract

Diffusible small molecule microbial hormones drastically alter the expression profiles of antibiotics and other drugs in actinobacteria. For example, avenolide (a butenolide) regulates production of avermectin, derivatives of which are used in the treatment of river blindness and other parasitic diseases. Butenolides and γ-butyrolactones control production of pharmaceutically important secondary metabolites by binding to TetR family transcriptional repressors. Here, we describe a concise, 22-step synthetic strategy for the production of avenolide. We present crystal structures of the butenolide receptor AvaR1 in isolation, and in complex with avenolide, as well as AvaR1 bound to an oligonucleotide derived from its operator. Biochemical studies guided by the co-crystal structures enable identification of 90 new actinobacteria that may be regulated by butenolides, two of which are experimentally verified. These studies provide a foundation for understanding regulation of microbial secondary metabolite production, which may be exploited for the discovery and production of novel medicines.

Article and author information

Author details

  1. Iti Kapoor

    Biochemistry, University of Illinois at Urbana-Champaign, Urbana, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Philip Olivares

    Department of Biochemistry, University of Illinois at Urbana-Champaign, Rockville, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3182-5884
  3. Satish K Nair

    Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, United States
    For correspondence
    s-nair@life.uiuc.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1790-1334

Funding

National Institutes of Health (GM131347)

  • Iti Kapoor

The funding agency provided support for facilities and services. The agency also provided partial salary support for all participants.

Reviewing Editor

  1. Jon Clardy, Harvard Medical School, United States

Publication history

  1. Received: April 14, 2020
  2. Accepted: June 6, 2020
  3. Accepted Manuscript published: June 8, 2020 (version 1)

Copyright

© 2020, Kapoor et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 851
    Page views
  • 119
    Downloads
  • 0
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Further reading

    1. Biochemistry and Chemical Biology
    2. Plant Biology
    Pengxiang Fan et al.
    Research Article
    1. Biochemistry and Chemical Biology
    2. Cell Biology
    Senem Aykul et al.
    Research Article Updated