What can phylogeny tell us about chemical diversity?

N Rønsted; GI Stafford; AW Meerow; G Petersen; J Van Staden; AK Jäger

doi:10.1055/s-0031-1282134

Planta Medica, Table of Contents

What can phylogeny tell us about chemical diversity?

N Rønsted ¹, GI Stafford ¹, AW Meerow ², G Petersen ³, J Van Staden ⁴, AK Jäger ⁵

¹Natural Products Research, Department of Medicinal Chemistry, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark; Present address: Botanical Gardens, Natural History Museum of Denmark, Sølvgade 83, Opg. S., DK-1307 Copenhagen, Denmark
²USDA, 13601 Old Cutler Road, Miami, Florida, USA
³Botanical Gardens, Natural History Museum of Denmark, Sølvgade 83, Opg. S., DK-1307 Copenhagen, Denmark
⁴University of KwaZulu-Natal, P/bag X01, 3209 Scottsville-Pietermaritzburg, South Africa
⁵Natural Products Research, Department of Medicinal Chemistry, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark

Abstract

Plant secondary metabolites are produced and selected by evolution for their biological activity. Such natural products have always played a major role in traditional medicine and as leads for modern medicine. Only a small fraction of the Worlds biodiversity has been explored for chemical and biological activity. A correlation between phylogeny and biosynthetic pathways is often assumed and could offer a predictive approach enabling more efficient selection of plants for traditional medicine lead discovery. However, formal tests of correlations between phylogeny and chemistry are rare, and the potential predictive power is consequently unknown. As a case in point, we are exploring the Amaryllidaceae subfamily Amaryllidoideae sensu APG, which is known for subfamily specific alkaloids with activity in the central nervous system (CNS). Galanthamine registered for the treatment of Alzheimer's disease was first isolated from the Caucasian snowdrop Galanthus woronowii Losinsk. We present a phylogenetic hypothesis of the Amaryllidaceae subfamily Amaryllidoideae based on nuclear, plastid and mitochondrial DNA sequences of over 100 of the circa 850 species, representing all tribes and geographical regions. All major lineages are now well supported and the extended sampling uncovered several genera as non-monophyletic, emphasizing the importance of using phylogenetic rather than classical classification for interpretation of character distribution. Alkaloid profiles and CNS-related bioactivity profiles are significantly correlated with phylogeny using formal tests. Relationships between phylogenetic and chemical diversity are further explored. The predictive power can be used to select candidate taxa for lead discovery and to make recommendations for traditional use.

Keywords: Amaryllidaceae, phylogeny, chemical diversity, lead discovery

Acknowledgement: This research was supported by a Steno grant (N°272–07–0281) to NR from the Danish Council for Independent Research – Natural Sciences.