Microscopic landscape inside a bacterial cell showing enzymes creating azetidine-2-carboxylic acid.

Decoding Nature's Tiny Factories: How Scientists Are Unlocking the Secrets of Bacterial Enzymes

Author's portrait.
Nico Varela in Science & Nature September 2025 • 4 min read.

"A new study reveals the intricate mechanism behind a bacterial enzyme that creates unusual amino acids, paving the way for novel drug development and synthetic biology applications."


For years, scientists have been captivated by the intricate world of enzymes, nature's tiny biological machines. Enzymes, particularly those known as methyltransferases (MTs), play a crucial role in modifying molecules within living organisms. These modifications can significantly alter the function and behavior of everything from DNA to proteins. Now, a groundbreaking study is shedding light on a previously unknown ability of a specific type of bacterial enzyme.

This research, recently published in ACS Chemical Biology, focuses on a class I methyltransferase called VioH, found in the bacterium Cysotobacter violaceus. What makes VioH so interesting is its ability to catalyze an unusual reaction: it cyclizes a molecule called S-adenosyl-L-methionine (SAM) to produce azetidine-2-carboxylic acid (AZE). This is a significant departure from the typical function of methyltransferases, which usually transfer methyl groups to other molecules.

The discovery that VioH can create AZE, which is a precursor to 4-methylazetidinecarboxylic acid (MAZ), a unique component found in vioprolides, opens new avenues for understanding natural product biosynthesis and potentially engineering new bioactive compounds. Vioprolides themselves are of interest for their antifungal and cytotoxic properties, and understanding how their building blocks are created is a crucial step towards harnessing their potential.

What Makes This Discovery So Important?

Microscopic landscape inside a bacterial cell showing enzymes creating azetidine-2-carboxylic acid.

The excitement surrounding this discovery stems from several factors. First, it reveals a novel biochemical pathway. The cyclization of SAM by VioH to form AZE was previously unknown for class I MTs, broadening our understanding of the enzymatic capabilities within this family. This discovery challenges the conventional understanding of how these enzymes function and opens up new avenues for research.

Second, the study provides insights into the biosynthesis of unusual amino acids. MAZ, the compound AZE is a precursor to, is a rare amino acid found in only a few natural products. Understanding how bacteria create these unusual building blocks can inspire scientists to design new ways to synthesize similar compounds in the lab.

  • Drug Discovery: Unusual amino acids like MAZ can be incorporated into drug candidates to improve their activity, stability, or ability to target specific tissues.
  • Synthetic Biology: Understanding the enzymatic machinery behind MAZ production allows scientists to engineer microorganisms to produce novel compounds or modify existing ones.
  • Understanding Natural Processes: This research helps us understand the complex chemical processes occurring in nature, particularly within bacteria, which are prolific producers of bioactive molecules.
Third, the research team was able to reconstitute the entire pathway for AZE and MAZ production in vitro. By combining VioH with another enzyme called VioG, they demonstrated the complete synthesis of MAZ, confirming the role of these enzymes in the biosynthetic pathway. This in vitro reconstitution is a powerful tool because it allows scientists to study the reaction in a controlled environment and manipulate the conditions to optimize product formation.

What's Next?

While this study provides a significant leap forward, there's still much to explore. Further research will focus on elucidating the detailed mechanism of VioH, identifying the specific amino acid residues involved in catalysis, and optimizing the production of AZE and MAZ. Ultimately, scientists hope to harness this knowledge to develop new drugs, engineer new biosynthetic pathways, and further unravel the mysteries of the microbial world.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

Everything You Need To Know

1

What are methyltransferases, and why are they important?

Methyltransferases (MTs) are enzymes that modify molecules within living organisms. They are significant because these modifications can alter the function and behavior of molecules like DNA and proteins. Understanding how MTs work can lead to advances in drug discovery and synthetic biology. For example, the class I methyltransferase VioH can cyclize S-adenosyl-L-methionine (SAM) to produce azetidine-2-carboxylic acid (AZE).

2

What is VioH, and what makes it so special?

VioH is a class I methyltransferase found in the bacterium Cysotobacter violaceus. Its significance lies in its ability to catalyze an unusual reaction, the cyclization of S-adenosyl-L-methionine (SAM) to produce azetidine-2-carboxylic acid (AZE). This is important because it deviates from the typical function of methyltransferases, which usually transfer methyl groups to other molecules, and opens new avenues for research into enzymatic capabilities.

3

What is azetidine-2-carboxylic acid (AZE), and why is it important? What is missing to make MAZ?

Azetidine-2-carboxylic acid (AZE) is significant because it is a precursor to 4-methylazetidinecarboxylic acid (MAZ), a unique component found in vioprolides, and its production by VioH expands our knowledge of biochemical pathways. Vioprolides are of interest because of their antifungal and cytotoxic properties. By understanding how AZE is created, scientists can better understand natural product biosynthesis and potentially engineer new bioactive compounds. The missing step from AZE to MAZ is catalyzed by another enzyme called VioG.

4

What does it mean to reconstitute the AZE and MAZ production pathway in vitro, and why is that important?

The in vitro reconstitution of the AZE and MAZ production pathway refers to recreating the entire biochemical pathway in a controlled laboratory setting. By combining VioH with another enzyme called VioG, scientists demonstrated the complete synthesis of MAZ. This is significant because it allows scientists to study the reaction in a controlled environment, manipulate conditions to optimize product formation, and confirm the roles of the enzymes involved in the biosynthetic pathway.

5

What are the potential applications of unusual amino acids like MAZ?

Unusual amino acids, like MAZ, have a range of potential applications. These applications include improving drug efficacy, stability, and tissue targeting in drug discovery. They also involve engineering microorganisms to produce novel compounds or modify existing ones in synthetic biology. Furthermore, studying these amino acids enhances our understanding of complex chemical processes within bacteria, which are prolific producers of bioactive molecules.

Newsletter Subscribe

Subscribe to get the latest articles and insights directly in your inbox.