Introduction
We are investigating the underexplored chemistry of Kunzea (kānuka / tea tree) in Aotearoa New Zealand in search of antimicrobial compounds and returning this knowledge of molecular basis of activity to Māori kaitiaki (guardians) of this taonga (treasured) species. The results of our investigation are being linked into innovative outreach activities that expand traditional offerings, fusing mātauranga (traditional knowledge), chemistry and biology to engage rangitahi (youth) in pūtaiao (science).
This paper reviews natural products from taonga plant species, with a particular focus on the New Zealand Myrtaceae representatives. Within NZ Myrtaceae, the bioactivity of mānuka, the most economically important species, is explored and contrasted with our current knowledge of kānuka bioactive natural products.
Novel natural products from taonga species of Aotearoa New Zealand
New Zealand has a unique range of flora species that have differentiated as a result of geological isolation from other landmasses,1 leading to a high degree of endemism in vascular plants. This distinct evolutionary lineage has allowed these species to develop unique bioactive natural products (with novel structures), which we can today study by isolation and identification.
Knowledge of natural products extends back to the first Māori in New Zealand, who encountered the fruit of the karaka tree – a novel species to Māori – and its highly poisonous seed. Mātauranga records a complex treatment of extended cooking and washing to leech the karakin alkaloid and make this into a nutritious and safe food source. With this decontamination knowledge, karaka was widely planted at Māori settlements around Aotearoa, establishing a reliable propagated food supply. In a similar vein, tutu (Coriaria spp.) was made into a refreshing drink, sweetener and jelly by straining the juice of the enfolding petals of the berry through toetoe or raupō flower heads – with multiple uses in healing and antiseptic applications. Failing to do this scrupulously enough caused acute poisoning from the neurotoxic tutin contained in all other plant parts.
A survey of New Zealand indigenous plant extracts showed widespread biological activity across sampled species, especially cytotoxic and antibacterial activities.2 Chemometric analysis of compounds from native New Zealand medicinal flora found 80% of the bioactive compounds were in known physicochemical drug space, and 10% to be lead-like. Therefore these compounds are well suited to further screening and drug development projects.3
Investigation of other taonga species has found numerous compounds with novel structures and properties. Horopito (Pseudowintera colorata) was found to have antibacterial, antifungal and insecticidal properties, among other bioactivities. A native mushroom (Iliodiction cibarium) used as a food source by Māori, contained uronic acids and an unusual, unresolved polysaccharide. Novel cannabinoids have also been identified in a liverwort (Radula marginata).
NZ Myrtaceae and valuable natural products
Myrtaceae is a large family of flowering plants with leaves containing oil glands that are a rich source of natural products, particularly acylphloroglucinols and phloroglucinol adducts. Familiar examples include Eucalyptus (gum trees) and mānuka. It comprises 121 genera and between 3800 and 5800 species, with a tropical-subtropical centre of diversity and reach extending into temperate Australasia.
Myrtaceae is a family known for producing secondary metabolites (essential oils) in oil glands, and has a rich history of ethnomedicinal use worldwide.4 This family has been fruitful in natural products chemistry worldwide, but is less investigated in New Zealand.
New Zealand is home to six indigenous genera of Myrtaceae (Fig. 1): Kunzea (approx. 10 species), Leptospermum (L. scoparium – two varieties), Lophomyrtus (L. bullata and L. obcordata), Metrosideros (12 endemic species), Neomyrtus (monotypic endemic genus - N. pedunculata), and Syzygium (one endemic species, S. maire).5 These indigenous species have high ecological, cultural and social value, and are iconic, such as pōhutukawa (Metrosideros excelsa), rātā (Metrosideros spp.), and mānuka (Leptospermum scoparium). Others, including Lophomyrtus bullata, contain unprecedented molecular frameworks.
Locally and internationally, mānuka honey is perhaps the most recognised and economically important example of a product from NZ Myrtaceae species. A 2020 MPI report estimated that the industry generated $374 million NZD in export revenue,6 representing a significant high-value sector and of particular note given the minimal manufacturing investment required. Mānuka honey contains MGO (methylglyoxal), derived from nectar, DHA (dihydroxyacetone) and other bioactives that provide antimicrobial activity beyond that of other floral honey. It remains a mystery, actively under investigation, why the DHA is present in mānuka honey.
Alongside this sits mānuka leaf oil, which is known to also be highly antimicrobial, but due to different compounds compared with honey. The bioactivity of mānuka oil varies extensively by regional chemotypes,7 with the best oil being sourced from the East Cape of the North Island. Currently demand is outstripping supply for this oil chemotype.8
This particular chemotype is enriched with the beta-triketones (Fig. 2), the class of antibacterial (and herbicidal) compounds in mānuka oil – especially leptospermone which is the major bioactive component.9 The β-triketones are considered to derive from polyketide biosynthetic pathways and are mainly found in plants within Myrtaceae. These bioactive structural moieties are commonly found as building blocks in more complex bioactive molecules across New Zealand and overseas Myrtaceae – often as adducts with other products of secondary metabolism (flavanones, monoterpenes and sesquiterpenes, for example).
While mānuka (oil and honey) has a clearly established chemotypic pattern and understanding of bioactivity, particularly antimicrobial activities, kānuka (Kunzea sp.) is underexplored in terms of bioactives chemistry. While there is evidence of some variation present in Kunzea, this has not been quantified to the same extent as mānuka owing to the lesser commercial interest in kānuka.
Mānuka vs kānuka
Kānuka (the Kunzea species complex in NZ) is similar in application and appearance10 to the related mānuka (Leptospermum scoparium – a botanically distinct species, like a plant cousin to kānuka), which contains several rare and bioactive compounds effective against bacteria, viruses, other plants, and some autoimmune conditions.10 While mānuka is relatively well characterised, kānuka remains much more of a mystery in terms of chemical composition, variation and even the number of species.
It is important to signal that while we as scientists may use binomial names and classifications, Māori do not necessarily distinguish these species in the same way: other names used include the generic ‘tea-tree’, kahikatea, red (L. scoparium) and white (Kunzea) mānuka;10 pronunciation also varies by dialect.
Mānuka and kānuka can be distinguished by their flowers/seeds and leaf morphology; mānuka have large, singular flowers/seeds, while kānuka have clusters of small flowers/seeds (Fig. 3).
The leaves of kānuka are also much softer and have a rounder tip compared to the sharply pointed leaf tips of mānuka (Fig. 4).
Kānuka (Kunzea sp.) are trees or shrubs in the Myrtaceae family endemic to New Zealand. Currently the Kunzea complex refers to a group of 10 recognised species defined on a genetic basis due to an extremely variable phenotype.11 Kānuka (Kunzea spp.) is botanically distinct from mānuka (Leptospermum scoparium); however, both species are Myrtaceae and valued by Māori, with these generally interchangeable (referred to as kahikatea or white and red mānuka) in rongoā (Māori traditional medicinal practice).9
Indigenous knowledge
A notable aspect of natural products chemistry is the utilisation of traditional knowledge to inform the choice of species for investigation. Combined with bioassay-directed isolation methods, using indigenous knowledge and traditional plants accelerates structural elucidation and understanding of the chemical ecology underlying macro-scale biological effects.
Indigenous knowledge in New Zealand is held within Mātauranga Māori, including rongoā (Māori medicinal practises), as a taonga of Māori. Engaging with the guardians of this knowledge is a privilege, representing a knowledge system developed from generations of lived experience across the motu. I am extraordinarily grateful to have this opportunity to work with Māori kaitiaki within my project, and I thank and acknowledge the significant role of iwi - as tangata whenua and kaitiaki of the taonga species we are privileged to work with - in my research as integral partners and research directors.
An example of this approach is presented in Lawrence et al.,12 who interwove Mātauranga Māori around kānuka to discover inhibitory activity against Phytophthora agathidicida (causative pathogen of Kauri dieback disease), highlighting the value gained from this intersection of bodies of knowledge. The authors emphasise that the findings are part of academic research, but the mātauranga and rongoā are taonga (treasures) belonging to tangata whenua, the indigenous people of Aotearoa.
Natural products of kānuka
Why kānuka? Kānuka has been used by Māori to treat a range of ailments and illness including viral infections – captured in the written record of traditional uses by Riley et al.10 Kānuka is widespread but little studied by natural product chemists, making it an exciting plant to study – particularly in the current climate of demand for novel antiviral compounds.
A chemotaxonomic analysis of Kunzea was undertaken in 1997, which found the essential oils were dominated by α-pinene (up to 67% of the oil).13 Further chemotaxonomic studies of kānuka identified a number of less volatile compounds that were expected to have bioactive properties.14 These included an array of compound classes covering various carbon and oxygen-containing frameworks, and conjugated derivatives of these.
Four antiviral acyl phloroglucinol derivatives structurally related to leptospermone have been identified from solvent extracts of K. sinclairii and K. ericoides.15 Recent work using Mātauranga Māori-guided screening found three new flavanones active against Phytophthora agathidicida, an oomycete pathogen that is the causative agent of kauri dieback.12 Hence we see that there is evidence of a diverse bioactive chemistry present in Kunzea species.
Using another widespread species, mānuka, outreach has been undertaken across NZ schools with herbicidal triketones and lettuce seeds as an interactive medium to explore Mātauranga Māori and this taonga species in terms of chemical ecology, nationwide variation and economic potential.16 The combination of community-based sampling and Plant & Food Research chemical analysis created complementary datasets that created scope for use across age and ability ranges up to year 13 students – with potential for subsequent investigations by interested students. This approach proved successful, especially for engaging Māori and rural students across NZ, with the assay, chemotype variation and visualisation proving key highlights for students and teaching staff.17 Building upon this, I aim to develop a complementary antimicrobial assay for use with kānuka extracts collected with schools.
Acknowledgements
This project is carried out in collaboration with landowners from Kāti Huirapa Rūnaka ki Puketeraki and Ngāti Porou. My sincere thanks go to all involved in my research for their support and advice.
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