Universiteit Leiden

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Research project

Biotransformation of plant metabolites in microorganisms

- How to deconvolute metabolic mixture of precursors and products by biontransformation? - How to optimize the reaction conditions to produce bioactive compounds in biotransformation? - What is the effect of co-treating fungi or bacteria for biotransformations?

2017 - 2021
Young Hae Choi
Conacyt National Council of Science and technology-Mexico Conacyt National Council of Science and technology-Mexico

Due to the enormous chemical diversity, natural products attracted great attraction for new drug development. Their complexity, however, is an obstacle for the development. Using the conventional approach combining bioactivity and chemical isolation, it takes a long time and high cost to find a bioactive chemical from complex moisture. Also, in the final stages, many bioactive natural products are discarded because of poor water solubility and non-desirable toxicity. A novel systematic approach is required to solve these problems.

In this project, metabolomics and biotransformation are applied to the investigation of chemical interaction between plants and microorganisms. Plant metabolites are biontransformed by enzymes, bacteria or fungi to increase chemical diversity, bioactivity, and water-solubility. The biotransformations are carried out with mixture of metabolites and deconvoluted by metabolomic profiling techniques.

Natural Products are the most plentiful resource of bioactive compounds but the complexity is a dilemma. Natural products have served as a plentiful resource for diverse fields of life science and industry. Even in these days, the importance of natural product is not diminished at all. Over 40% of new chemicals are still obtained from natural resource. The attraction of natural products research, as a material science in biology, lies in their unsurpassed diversity providing an enormous number of chemicals for screening. However, there is a dilemma in the diversity. Due to innate variety and dynamic change of metabolites levels in living organisms, profiling all or desired group of metabolites is a great challenge. Particularly, in drug development from natural resources, the complexity retards the development so that finding a new active compound from natural resource by classical methods is painstakingly slow, due to their low concentrations or interference of other co-existed compounds. The diversity of both chemicals and organisms as well as biological variation, the bright side of natural products, can easily become a dark side, complexity, which is the first hurdle tackled by natural products researchers.

Metabolomics combined with Biotransformation can be the solution to Handle Natural Products Resource. A possible solution might be provided by metabolomics, which allows the comprehensive profiling of all the metabolites. Recently, the trend in life science has shifted to a more holistic or systems approach, observing organisms as a whole. Systems biology aims to do this by observing all the components of living organisms and how they interact. Diverse omics technologies such as genomics, transcriptomis, proteomics and metabolomics are part of systems biology. Metabolomics is one of the most recent omics technologies and in the last couple of years it has been increasingly applied to many fields of biological science such as drug development, functional genomics, physiology, toxicology, and natural products research. Indeed, metabolomics uses one part to provide holistic information of the whole metabolome network. Recent advances in analytical chemistry, combined with multivariate data analysis, brought us closer to the final goal of metabolomics, comprehensive evaluation of all metabolites in living organisms.

To develop a proper prodrug from natural resources profiling using metabolomics techniques is not enough. Most active compounds are in low level in organisms and their bioactivity can be improved by chemical modifications. Increasing their water-solubility-a common obstacle for compounds isolated from natural resources and reducing possible toxicity can also be achieved by these modifications. In this project, we propose to apply biotransformation processes using enzymes and microorganisms. Biotransformation can be defined as the enzymatic conversion of chemicals into substances having specifically modified structures. Many previous studies report successful results in the conversion of chemicals to others with more pharmacological activity, or stronger bioactivities in general, low toxicity, and higher water-solubility. Thus, based on metabolomics findings we will detect bioactive metabolites. These active compounds will be further modified by enzymes or microorganisms in order to provide more pharmacologically useful prodrugs.

General overview of biotransformation project.
  • Are Natural Deep Eutectic Solvents the Missing Link in Understanding Cellular Metabolism and Physiology? Y. H. Choi, J. van Spronsen, Y. Dai, M. Verberne, F. Hollmann, I. W. C. E. Arends, G.-Jan Witkamp, R. Verpoorte. Plant Physiology, 156, 1701-1705, 2011
  • Natural Deep Eutectic Solvents as New Potential Media for Green Technology. Y. Dai, J. van Spronsen, G. -J. Witkamp, R. Verpoorte, Y. H. Choi. Analytica Chimica Acta, 766, 61-68, 2013.
  • Natural deep eutectic solvents as a new extraction media for phenolic metabolites in Carthamus tinctorius L. Y. Dai, G. –J. Witkamp, R. Verpoorte, Y. H. Choi. Analytical Chemistry, 85, 6272-6278, 2013.
  • Natural deep eutectic solvents providing enhanced stability of natural colarants from safflower (Carthamus tinctorius). Y. Dai, R. Verpoorte, Y. H. Choi. Food Chemistry, 159, 116-121, 2014.
  • Tailoring properties of natural deep eutecic solvents with the addition of water to facilitate their applications. Y. Dai, R. Verpoorte, G. –J. Witkamp, Y. H. Choi. Food Chemistry, 187, 14-19, 2015
  • Extending pharmaocological dose-response curves for salsalate with natural deep eutectic solvents. E. Rozema, A. D. van Dam, H. C. M. Sips, R. Verpoorte, O. C. Meijer, S. Kooijman, Y. H. Choi. RSC Advances, 5, 61398-61401, 2015.
  • Application of natural deep eutectic solvents to the extraction of anthocyanins from Catharanthus roseus with high extractability and stability replacing conventional organic solvent. Y. Dai, E. Rozema, R. Verpoorte, Y. H. Choi. Journal of Chromatography A, 1434, 50-56, 2016.
  • Application of natural deep eutectic solvents to the extraction of vanillin as a green processing. C. G. Gonzalez, N. R. Mustafa, E. G. Wilson, R. Verpoorte, Y. H. Choi. Flavour and Fragrance Journal, in press, 2017
  • Towards eco-friendly crop protection: natural deep eutectic solvents and defensive secondary metabolites. S. Mouden . P. G. L. Klinkhamer . Y. H. Choi . K. A. Leiss. Phytochemistry Reviews, in press, 2017
  • Ionic liquids and deep eutectic solvents in natural products research. Y. Dai, J. van Spronsen, G. –J. Witkamp, R. Verpoorte, Y. H. Choi. Journal of Natural Products, 76, 2162-2173, 2013.
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