Liquid Extraction Based Ambient Ionization Mass Spectrometry in Natural Product Discovery

We had the pleasure of speaking with Jess Deng, a fourth-year PhD candidate at Queen's University in Canada. Jess's research focuses on applying ambient ionization mass spectrometry techniques to streamline the natural product discovery process, particularly in fungal secondary metabolism.

Revolutionizing Natural Product Discovery

Jess's work aims to introduce a crucial step in the natural product discovery pipeline, addressing some of the field's most pressing challenges. Traditional methods of natural product discovery can be incredibly time-consuming and resource-intensive, often taking up to two years to identify a single compound - which may turn out to have been previously discovered.

To tackle this issue, Jess employs a liquid microjunction surface sampling probe (LMJ SSP), an ambient ionization technique that allows for rapid screening of fungal cultures grown under various conditions. This method enables researchers to prioritize potentially novel compounds before investing significant time and resources into bulk cultivation and extensive chromatographic separation.

The LMJ SSP Advantage

The LMJ SSP offers several advantages over conventional mass spectrometry approaches in this context:

1. Minimal sample preparation:  Unlike traditional methods requiring extensive extraction and purification steps, the LMJ SSP allows for direct sampling of fungal cultures.

2. Rapid analysis:  Jess reported being able to analyze 24-well plates with 13 different growth conditions in just 6 hours, using only 150 mL of solvent.

3. Early detection of novel metabolites:  By quickly identifying known compounds, researchers can focus their efforts on potentially new and interesting metabolites.

Exploring Fungal Metabolism

Jess's research explores how various environmental factors influence fungal secondary metabolism. Some key findings include:

1. Light conditions: Growth under white and amber light can decrease the production of certain fungal metabolite classes, including aromatic polyketides, sesquiterpenoids, and prenylated indole alkaloids.

2. Nitrogen sources:  The addition of 1.00% NH₄Cl to growth media affected the production of certain metabolites, such as tryptoquivaline A.

3. Co-culture experiments:  Jess is also investigating how fungi behave when grown alongside other organisms, potentially triggering the production of novel compounds.

Data Analysis Challenges

One of the unique challenges Jess faces is adapting existing data analysis tools to work with the LMJ SSP output. Many algorithms are designed for liquid chromatography (LC) data, requiring some creative problem-solving:

"A lot of my thesis is spent tricking algorithms into thinking that I'm doing an LC run when it's not," Jess explained. "So that's been quite interesting and I've found pretty unique ways of approaching that."

Validation and Future Directions

While the LMJ SSP technique shows promise for rapid screening, Jess acknowledges the ongoing debate regarding validation through chromatography. She believes that for quantitative analysis, traditional chromatographic methods still hold an edge. However, for screening applications, the speed and efficiency of the LMJ SSP make it a valuable tool.

Future work in this area could explore:

1. Additional environmental factors affecting fungal metabolism
2. Automation of the screening process
3. Application to other microorganisms beyond fungi

Beyond the Lab: A Smithsonian Adventure

Jess also shared her experience as a pre-doctoral fellow at the Smithsonian Museum of Conservation in Washington, D.C. There, she developed an assay using another ambient ionization technique, coded blade spray, to detect formaldehyde traces in fluid-preserved specimens. This project highlighted the potential applications of ambient ionization techniques beyond natural product discovery, demonstrating their versatility in addressing real-world challenges.

Conclusion

Jess Deng's innovative approach to natural product discovery showcases the potential of ambient ionization mass spectrometry techniques to revolutionize the field. By combining rapid screening methods with machine learning algorithms, researchers may soon be able to explore the vast untapped potential of fungal secondary metabolites more efficiently than ever before.

As the field of natural product discovery continues to evolve, techniques like the LMJ SSP may play an increasingly important role in identifying novel compounds with potential applications in pharmaceuticals, biofuels, and beyond.

The American Society for Mass Spectrometry (ASMS) Conference is one of the most significant annual events in the field of mass spectrometry, bringing together thousands of scientists, researchers, and industry professionals from around the world. The 2024 ASMS Conference, where I had the pleasure of meeting Jess Deng, took place from June 2-6 at the Anaheim Convention Center in California. This prestigious event typically attracts over 6,000 attendees and features more than 2,500 presentations, including talks and poster sessions.

Jess was presenting her innovative research on applying ambient ionization mass spectrometry techniques to streamline the natural product discovery process, particularly in fungal secondary metabolism. Her poster, which detailed the use of a liquid microjunction surface sampling probe (LMJ SSP) for rapid screening of fungal cultures, caught my attention due to its potential to revolutionize the field of natural product discovery.

ASMS conferences are known for fostering collaborations and providing a platform for researchers to showcase their latest work in mass spectrometry and allied topics. The event features a wide range of activities, including oral sessions, poster presentations, workshops, and corporate exhibitions. For early-career scientists like Jess, ASMS offers invaluable opportunities to network with peers, learn about cutting-edge technologies, and gain exposure for their research. Our chance meeting at ASMS 2024 exemplifies the conference's role in connecting researchers and facilitating the exchange of ideas in the mass spectrometry community.