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Biotechnol Adv. 2014 Nov 1;32(6):1180-204. doi: 10.1016/j.biotechadv.2014.03.001. Epub 2014 Mar 17.

Metabolite induction via microorganism co-culture: a potential way to enhance chemical diversity for drug discovery.

Author information

1
School of Pharmaceutical Sciences, EPGL, University of Geneva, University of Lausanne, quai Ernest-Ansermet 30, CH-1211 Geneva 4, Switzerland; Groupe Mer, Molécules, Santé-EA 2160, Faculté des Sciences pharmaceutiques et biologiques, Université de Nantes, 9 rue Bias, BP 53508, F-44035 Nantes Cedex 01, France.
2
School of Pharmaceutical Sciences, EPGL, University of Geneva, University of Lausanne, quai Ernest-Ansermet 30, CH-1211 Geneva 4, Switzerland.
3
Mycology and Biotechnology group, Institute for Plant Production Sciences IPS, Agroscope, Route de Duillier 50, P.O. Box 1012, 1260 Nyon, Switzerland.
4
School of Pharmaceutical Sciences, EPGL, University of Geneva, University of Lausanne, quai Ernest-Ansermet 30, CH-1211 Geneva 4, Switzerland. Electronic address: jean-luc.wolfender@unige.ch.

Abstract

Microorganisms have a long track record as important sources of novel bioactive natural products, particularly in the field of drug discovery. While microbes have been shown to biosynthesize a wide array of molecules, recent advances in genome sequencing have revealed that such organisms have the potential to yield even more structurally diverse secondary metabolites. Thus, many microbial gene clusters may be silent under standard laboratory growth conditions. In the last ten years, several methods have been developed to aid in the activation of these cryptic biosynthetic pathways. In addition to the techniques that demand prior knowledge of the genome sequences of the studied microorganisms, several genome sequence-independent tools have been developed. One of these approaches is microorganism co-culture, involving the cultivation of two or more microorganisms in the same confined environment. Microorganism co-culture is inspired by the natural microbe communities that are omnipresent in nature. Within these communities, microbes interact through signaling or defense molecules. Such compounds, produced dynamically, are of potential interest as new leads for drug discovery. Microorganism co-culture can be achieved in either solid or liquid media and has recently been used increasingly extensively to study natural interactions and discover new bioactive metabolites. Because of the complexity of microbial extracts, advanced analytical methods (e.g., mass spectrometry methods and metabolomics) are key for the successful detection and identification of co-culture-induced metabolites. This review focuses on co-culture studies that aim to increase the diversity of metabolites obtained from microbes. The various strategies are summarized with a special emphasis on the multiple methods of performing co-culture experiments. The analytical approaches for studying these interaction phenomena are discussed, and the chemical diversity and biological activity observed among the induced metabolites are described.

KEYWORDS:

Antimicrobials; Co-culture; Gene cluster activation; Interspecies communication; Mass spectrometry; Metabolomics; Microbiome; Microorganisms; Mixed fermentation; Natural products

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