Related Experiment Video

Updated: Apr 30, 2026

Mass Spectrometry-Guided Genome Mining as a Tool to Uncover Novel Natural Products
11:13

Mass Spectrometry-Guided Genome Mining as a Tool to Uncover Novel Natural Products

Published on: March 12, 2020

10.5K

Genome Mining Reveals Protease-Inhibitory Idioviridin Featuring Dual-Cascaded ATP-Grasp Ligases in Lactone Ring

Yueqian Li1, Liujie Huo1

  • 1State Key Laboratory of Microbial Technology, Shandong University, Qingdao, Shandong 266237, People's Republic of China.

ACS Chemical Biology
|April 29, 2026
PubMed

Insights

Researchers discovered hexacyclic idioviridin, a novel microviridin, synthesized through a unique enzymatic cascade involving three ATP-grasp ligases. This finding expands knowledge of RiPP enzymology and offers potential for bioengineering and therapeutics.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Natural Products Chemistry

Background:

  • Microviridins are ribosomally synthesized peptides with complex cage-like structures.
  • Their biosynthesis involves ATP-grasp ligases mediating lactone and lactam ring formations.

Purpose of the Study:

  • To investigate an unusual microviridin-like gene cluster.
  • To elucidate the biosynthesis and enzymatic mechanisms of a novel microviridin, idioviridin.

Main Methods:

  • Heterologous expression of a gene cluster encoding three ATP-grasp ligases and a precursor peptide.
  • Proteolytic processing and MS/MS analysis of intermediates.
  • Enzymatic activity assays and structural characterization.

Main Results:

  • Identification and characterization of hexacyclic idioviridin, a dual-core microviridin with six rings.
  • Elucidation of a hierarchical enzymatic pathway involving three ATP-grasp ligases (IdiD2, IdiD1, IdiC) in a cascaded manner.
  • Demonstration of novel catalytic directionalities and the first instance of two ATP-grasp ligases forming multiple lactone rings in microviridin biosynthesis.
  • Idioviridin showed potent inhibition of elastase and chymotrypsin.

Conclusions:

  • The study expands the known structural and enzymatic diversity of microviridins.
  • Provides novel insights into RiPP enzymology, particularly the function and substrate specificity of ATP-grasp ligases.
  • Highlights idioviridin's potential for bioengineering and therapeutic applications due to its potent protease inhibitory activity.

More Related Videos

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors10:33

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors

Published on: October 26, 2015

10.9K
Using Phage Display to Develop Ubiquitin Variant Modulators for E3 Ligases06:30

Using Phage Display to Develop Ubiquitin Variant Modulators for E3 Ligases

Published on: August 27, 2021

2.6K

Related Concept Videos

Pinching-off of Coated Vesicles01:32

Pinching-off of Coated Vesicles

Vesicle budding is orchestrated by distinct cytosolic proteins such as adaptor proteins, coat proteins, and GTPases. To initiate vesicle budding, membrane-bending proteins containing crescent-shaped BAR domains bind to the lipid heads in the bilayer and distort the membrane to form a protein-coated vesicle bud. Adaptors proteins such as AP2 for clathrin-coated vesicles can nucleate on the deformed membrane. Finally, coat proteins such as clathrin or COPI and COPII assemble into a coat forming...
3.1K
Inhibitors of Viral Protein Synthesis01:30

Inhibitors of Viral Protein Synthesis

Protein synthesis is indispensable for viral replication, as viruses lack the cellular machinery required for this process and must hijack the host's translational apparatus. In response, host cells deploy a critical innate immune defense involving interferons, specialized cytokines that play a central role in inhibiting viral propagation.Upon viral detection, infected cells release interferons that bind to receptors on adjacent uninfected cells, activating the JAK-STAT signaling pathway and...
58
Inhibitors of Bacterial DNA Synthesis01:28

Inhibitors of Bacterial DNA Synthesis

Bacterial pathogens depend on precise and efficient DNA replication to sustain infection. Two type II topoisomerases—DNA gyrase and topoisomerase IV—are critical to this process, as they resolve DNA supercoiling and unlink chromosomes during replication. Fluoroquinolones, synthetic derivatives of quinolones, exploit this mechanism by stabilizing the transient DNA–enzyme cleavage complex, preventing strand religation, and causing lethal double-strand breaks. These...
128