Plant secretory structures: more than just reaction bags
Graphical abstract
Introduction
Plants are known to be masters at generating chemical diversity. One invoked reason for this extraordinary diversity is their sessile nature. Being unable to escape adverse conditions, plants have evolved various processes to compensate for this immobility, one of them being the production of compounds that will protect them against aggressors or an unfavourable environment. An argument often used in articles about the biosynthesis of plant secondary metabolites to justify the work is that by elucidating the biosynthesis pathway it will become possible to make them more readily available by engineering easily cultivable microorganisms such as Escherichia coli or the yeast Saccharomyces cerevisiae. While this argument may hold true for substances produced by rare, endangered or difficult to cultivate species, or for substances that are in particularly low amounts such as Taxol, in many cases the substances of interest are actually present in fairly large quantities in the plant. In Table 1, some examples are given that illustrate this point.
This capacity to produce specialized metabolites in large quantities means that developing processes based on metabolic engineering and fermentation of microorganisms is a tough challenge. A revealing story in this regard is that of the engineering of artemisinic acid, the precursor of the antimalarial artemisinin in yeast. In a series of remarkable metabolic engineering efforts, production of artemisinic acid in yeast reached over 20 g/L [2, 3, 4]. The industrial development of this process was taken over by a non-profit organization and ultimately by the pharmaceutical giant Sanofi-Aventis [5]. Major investments were made in a production facility to supply this compound for the manufacture of anti-malarial medication. However, the production costs were still above those of plant-produced artemisinin and a better organization of artemisinin production by small farmers led to a stabilization of the prices and of the supply. This rendered the fermented route no longer competitive. The production plant was sold, and is now faced with an uncertain future [6•]. The lesson of this is that plants can be hard to beat and that it may be worth understanding how they manage to achieve this high productivity. There have been efforts to try and exploit this inherent capacity for metabolic engineering purposes to develop the production of industrial compounds in plants. Current efforts and perspectives for the production of isoprenoids in plant cell factories are reviewed in this issue [7]. The combination of large scale sequencing data, particularly from non-model species, and of recent developments in synthetic biology such as modular assembly schemes based on Golden Gate cloning [8, 9], create exciting opportunities for the production of secondary metabolites in plants. In this regard, one nice and recent example is the gram-scale production of triterpenoids in Nicotiana benthamiana [10].
Many, if not all, plant species possess dedicated organs or tissues where these metabolites are produced and stored, typically in large quantities. These specialized structures can be classified in two major classes based on their localization in the plant: at the surface or internal. At the surface, probably the most broadly represented type of secretory structures are glandular trichomes. They can adopt a myriad of shapes and sizes but have in common the capacity to synthesize large quantities of metabolites and to secrete them at the surface or store them in dedicated compartments depending on the nature of the compounds [11].
Inside the plant, a number of secretory structures or specialized cells dedicated to the biosynthesis and storage of metabolites have been described. These include laticifers, resin ducts, secretory cavities and oil glands. These structures have evolved to accumulate and store large quantities of metabolites or polymers. The purpose of this review is to survey the latest knowledge in our understanding of how these specialized structures work, specifically what are the metabolic features that allow these structures to be so productive. Because most of the work in this area is on glandular trichomes, the content of this review will be strongly biased on these organs.
Section snippets
Transcriptional activation of committed pathways and occurrence of specific isoforms
Probably the clearest feature of secretory structures accumulating a particular class of compounds, is the high transcriptional activation of genes encoding enzymes of the committed pathways for these compounds. In most cases, the compounds which accumulate in these organs are also synthesized there, explaining these high expression levels. For example, in glandular trichomes, this has been a tremendous help to identify and characterize a number of pathways, including those of menthol in
Where do glandular trichomes get their carbon and energy from?
The massive productivity of glandular trichomes for hydrocarbon compounds raises the question of the origin of the carbon and of the energy and reducing power required to drive these biosyntheses. Here, a distinction should be made between green (or photosynthetic) and non-photosynthetic trichomes. Typically peltate trichomes of the Lamiaceae (mint family) are non-photosynthetic [57]. Early labelling studies in peppermint indicated that glucose could be incorporated into terpenes [58]. It was
Does refixation of CO2 via C4 metabolism increase photosynthetic trichome productivity?
Mining of the transcriptome and proteome data revealed that genes typically associated with C4-photosynthesis are overexpressed in tomato trichomes, in particular phosphoenolpyruvate carboxykinase (PEPCK) and plastidial NADP-dependent malate dehydrogenase [41••]. Although PEPCK is typically described as a decarboxylating enzyme involved in gluconeogenesis, it is a reversible enzyme which has high affinity for CO2 at physiological concentrations of cations [64]. Furthermore, one can assume that
Conclusion
The extraordinary capacity of plants to produce large amounts of metabolites in specialized secretory structures is beginning to be unravelled. In addition to high expression levels of committed pathways, dedicated central and energy metabolic networks have evolved to optimize precursor supply and carbon-efficiency. These include the expression of specific enzyme isoforms with adapted kinetic properties or regulatory mechanisms. Interestingly, photosynthetic trichomes are largely auxotrophic
Conflict of interest
The author declares no conflicts of interest.
References and recommended reading
Papers of particular interest, published within the period of review, have been highlighted as:
• of special interest
•• of outstanding interest
Acknowledgements
The author gratefully acknowledges the support of the Deutsche Forschungsgemeinschaft (Grant TI800/1-1) and of the Leibniz-Institute of Plant Biochemistry.
I apologize to those whose work was not cited for space reasons.
References (75)
Glandular trichomes: what comes after expressed sequence tags?
Plant J
(2012)- et al.
Functional genomics and the biosynthesis of artemisinin
Phytochemistry
(2007) Making artemisinin
Phytochemistry
(2008)- et al.
The molecular cloning of artemisinic aldehyde Delta 11(13) reductase and its role in glandular trichome-dependent biosynthesis of artemisinin in Artemisia annua
J Biol Chem
(2008) - et al.
Monoterpenes in the glandular trichomes of tomato are synthesized from a neryl diphosphate precursor rather than geranyl diphosphate
Proc Natl Acad Sci U S A
(2009) - et al.
Regiospecific cytochrome P450 limonene hydroxylases from mint (Mentha) species: cDNA isolation, characterization, and functional expression of (−)-4S-limonene-3-hydroxylase and (−)-4S-limonene-6-hydroxylase
Arch Biochem Biophys
(1999) - et al.
Hydroxylation of limonene enantiomers and analogs by recombinant (−)-limonene 3- and 6-hydroxylases from mint (Mentha) species: evidence for catalysis within sterically constrained active sites
Arch Biochem Biophys
(2001) - et al.
Monoterpene double-bond reductases of the (−)-menthol biosynthetic pathway: isolation and characterization of cDNAs encoding (−)-isopiperitenone reductase and (+)-pulegone reductase of peppermint
Arch Biochem Biophys
(2003) - et al.
(−)-Menthol biosynthesis and molecular genetics
Naturwissenschaften
(2005) - et al.
Programming cells by multiplex genome engineering and accelerated evolution
Nature
(2009)
Chlorsulfuron modifies biosynthesis of acyl acid substituents of sucrose esters secreted by tobacco trichomes
Plant Physiol
Studies of the site and mode of biosynthesis of tobacco trichome exudate components
Arch Biochem Biophys
Light enables a very high efficiency of carbon storage in developing embryos of rapeseed
Plant Physiol
Phosphoenolpyruvate carboxykinase assayed at physiological concentrations of metal ions has a high affinity for CO2
Plant Physiol
Improving peppermint essential oil yield and composition by metabolic engineering
Proc Natl Acad Sci U S A
High-level production of amorpha-4,11-diene, a precursor of the antimalarial agent artemisinin, in Escherichia coli
PLoS ONE
Production of amorphadiene in yeast, and its conversion to dihydroartemisinic acid, precursor to the antimalarial agent artemisinin
Proc Natl Acad Sci U S A
High-level semi-synthetic production of the potent antimalarial artemisinin
Nature
Semi-synthetic artemisinin: a model for the use of synthetic biology in pharmaceutical development
Nat Rev Microbiol
Synthetic biology's first malaria drug meets market resistance
Nature
Creating plant molecular factories for industrial and nutritional isoprenoid production
Curr Opin Biotechnol
A golden gate modular cloning toolbox for plants
ACS Synth Biol
Standards for plant synthetic biology: a common syntax for exchange of DNA parts
New Phytol
A translational synthetic biology platform for rapid access to gram-scale quantities of novel drug-like molecules
Metab Eng
An investigation of the storage and biosynthesis of phenylpropenes in sweet basil
Plant Physiol Biochem
Differential production of meta hydroxylated phenylpropanoids in sweet basil peltate glangular trichomes and leaves is controlled by the activities of specific acyltransferase and hydeoxylases
Plant Physiol
Characterization of phenylpropene O-methyltransferases from sweet basil: facile change of substrate specificity and convergent evolution within a plant O-methyltransferase family
Plant Cell
The biochemical and molecular basis for the divergent patterns in the biosynthesis of terpenes and phenylpropenes in the peltate glands of three cultivars of basil
Plant Physiol
Characterization of geraniol synthase from the peltate glands of sweet basil
Plant Physiol
Eugenol and isoeugenol, characteristic aromatic constituents of spices, are biosynthesized via reduction of a coniferyl alcohol ester
Proc Natl Acad Sci U S A
Chavicol formation in sweet basil (Ocimum basilicum): cleavage of an esterified C9 hydroxyl group with NAD(P)H-dependent reduction
Org Biomol Chem
Characterization of two genes for the biosynthesis of the labdane diterpene Z-abienol in tobacco (Nicotiana tabacum) glandular trichomes
Plant J
A novel pathway for sesquiterpene biosynthesis from Z,Z-farnesyl pyrophosphate in the wild tomato Solanum habrochaites
Plant Cell
Artemisia annua L. (Asteraceae) trichome-specific cDNAs reveal CYP71AV1, a cytochrome P450 with a key role in the biosynthesis of the antimalarial sesquiterpene lactone artemisinin
FEBS Lett
Identification of a BAHD acetyltransferase that produces protective acyl sugars in tomato trichomes
Proc Natl Acad Sci U S A
Functionally divergent alleles and duplicated loci encoding an acyltransferase contribute to acylsugar metabolite diversity in Solanum trichomes
Plant Cell
In vitro reconstruction and analysis of evolutionary variation of the tomato acylsucrose metabolic network
Proc Natl Acad Sci U S A
Cited by (30)
Detoxification of monoterpenes by a family of plant glycosyltransferases
2022, PhytochemistryCitation Excerpt :Therefore, plants store monoterpenes in specialized compartments and/or cell types. Examples of such storage tissues include idioblasts, glandular trichomes, resin ducts and secretory cavities (Lange, 2015; Tissier, 2018). Menthol is deposited in peltate-type glandular trichomes (Croteau et al., 2005).
The ins and outs of transporters at plasma membrane and tonoplast in plant specialized metabolism
2022, Natural Product ReportsControl of resource allocation between primary and specialized metabolism in glandular trichomes
2022, Current Opinion in Plant BiologyCitation Excerpt :CO2 refixation has also been reported in nonfoliar tissues of several plant species where usually stomatal density is lower [52]. Furthermore, genes typically associated with C4-photosynthesis such as phosphoenolpyruvate carboxylase and phosphoenolpyruvate carboxy kinase that are enriched in GTs of cannabis and tomato respectively, could also be acting in a C concentrating mechanism refixing CO2 in the form of C4-acids minimizing C loss [40,43]. On the other hand, although the expression of NtRbcS-T is restricted to the glandular cells of the trichomes of tobacco, genes of mesophyll-related RbcS are expressed at levels three and six times higher than those of the T-type subunit [17].
Effects of light intensity on the anatomical structure, secretory structures, histochemistry and essential oil composition of Aeollanthus suaveolens Mart. ex Spreng. (Lamiaceae)
2021, Biochemical Systematics and EcologyCitation Excerpt :The biosynthesis and accumulation of essential oils can vary according to sites, such as leaves, stem and root and usually occur in specialized structures, such as glandular trichomes (Lamiaceae, Verbenaceae and Asteraceae), differentiated parenchymal idioblasts (Poaceae, Lauraceae, and Piperaceae), lysigenous, schizolysigenous and schizogenous cavities. ( Pinaceae and Rutaceae), and oil channels (Apiaceae) (Tissier, 2018). Secretory trichomes are considered the primary secretory site of essential oils in Lamiaceae species and present a great diversity in morphological types and secondary metabolite classes.
Genetic Control of Glandular Trichome Development
2020, Trends in Plant ScienceCitation Excerpt :For example, Ro et al. [7] reported the production of the arteminisin antimalarial drug precursor artemisinic acid in yeast. However, artemisinin world supply still mainly relies on extraction from Artemisia annua [8–10]. The amount of specialized metabolites produced by a plant is often tightly correlated to the density of glandular trichomes present at the surface of the epidermis [8,11–14].
Role of metabolites in abiotic stress tolerance
2020, Plant Life under Changing Environment: Responses and Management