Microbial metabolomics in open microscale platforms

• Published in: Nature communications Vol. 7; no. 1; p. 10610
• Main Authors: Barkal, Layla J., Theberge, Ashleigh B., Guo, Chun-Jun, Spraker, Joe, Rappert, Lucas, Berthier, Jean, Brakke, Kenneth A., Wang, Clay C. C., Beebe, David J., Keller, Nancy P., Berthier, Erwin
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 04.02.2016; Nature Publishing Group; Nature Portfolio
• Subjects: 13/62; 14/63; 631/326/2522; 631/45/320; 631/92; Aspergillus - metabolism; Aspergillus flavus - metabolism; Aspergillus fumigatus - metabolism; Aspergillus nidulans - metabolism; Chromatography, High Pressure Liquid; Coculture Techniques; Culture; Culture Techniques; Fungi; Fusarium - metabolism; Humanities and Social Sciences; Interfaces; Liquid-liquid extraction; Mass spectrometry; Mass spectroscopy; Metabolism; Metabolites; Metabolome; Metabolomics; Metabolomics - methods; Microenvironments; Microfluidics; Microorganisms; multidisciplinary; Natural products; Organic chemistry; Organic solvents; Platforms; Pseudomonas aeruginosa - metabolism; Ralstonia solanacearum - metabolism; Science; Science (multidisciplinary); Secondary metabolites; Tandem Mass Spectrometry
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms10610

The microbial secondary metabolome encompasses great synthetic diversity, empowering microbes to tune their chemical responses to changing microenvironments. Traditional metabolomics methods are ill-equipped to probe a wide variety of environments or environmental dynamics. Here we introduce a class of microscale culture platforms to analyse chemical diversity of fungal and bacterial secondary metabolomes. By leveraging stable biphasic interfaces to integrate microculture with small molecule isolation via liquid–liquid extraction, we enable metabolomics-scale analysis using mass spectrometry. This platform facilitates exploration of culture microenvironments (including rare media typically inaccessible using established methods), unusual organic solvents for metabolite isolation and microbial mutants. Utilizing Aspergillus , a fungal genus known for its rich secondary metabolism, we characterize the effects of culture geometry and growth matrix on secondary metabolism, highlighting the potential use of microscale systems to unlock unknown or cryptic secondary metabolites for natural products discovery. Finally, we demonstrate the potential for this class of microfluidic systems to study interkingdom communication between fungi and bacteria. Traditional methods for microbial culture and subsequent metabolomics are time-consuming and labour-intensive. Here the authors present a microscale culture platform with integrated extraction for efficient, low-volume metabolomics of relevant microenvironments and microbial co-cultures.