Lignans: Insights into Their Biosynthesis, Metabolic Engineering, Analytical Methods and Health Benefits

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Background

Lignans encompass a large and complex group of phytochemicals widely distributed throughout terrestrial plant lineages. Lignans play important roles in both plant ecology (interactions with and adaptation to an ever-changing environment) and physiology/ development. As their specialized metabolite nature might suppose, lignans have been related to plant defense against a number of herbivores and microorganisms. For example, their constitutive deposition helps impart durability, longevity, and resistance to the heartwoods of many tree species against wood-rotting fungi, therefore acting as phytoanticipins. Lignans can also act as phytoalexins, being synthesized de novo by plants accumulating quickly at areas of pathogen or herbivore attack. However, the precise roles in planta and the ecological significances of most lignans are still not well established.

As for many biologically active compounds originating from plants, lignan exploration has not been restricted solely to the plant research field but has also triggered intensive studies in the fields of human diet and/or health research over the last decades. Some lignans, belonging to the phytoestrogen class are converted, upon ingestion, by human gastrointestinal microbiota into the mammalian lignans enterodiol and enterolactone. The latter display the well-described chemopreventive properties against various tumors (such as breast, colon and prostate cancers) or cardiovascular disorders, whereas some other studies also report their roles in preventing diabetes. Other lignans are already used in pharmacy and medicine such as podophyllotoxin, the natural starting compound for the synthesis of lead anticancer drugs (Etoposide, Teniposide, Etopophos). However, many questions remain concerning i) their bioconversion, pharmacokinetic, and molecular targets, etc. and ii) in simply searching for their perennial and viable sources for human health applications.

From a biosynthetic point of view, many lignans are formed by the oxidative coupling of E-coniferyl alcohol moieties. But gene identification, gene regulation or biosynthetic enzyme characterization study are still scarce. For example, lignans can share the same precursor as for lignins, the complex polymers that provide rigidity and support to the vascular plants. The regulation of the genes specifically related to lignan biosynthesis or the precursor partition between lignin and lignans have only rarely been investigated. Such data though could yield not only information about the role of these compounds but also for optimizing their bioproduction using metabolic engineering strategies.

Their chemical nature, structural features, physicochemical behavior, and concentrations greatly differ from various plant organs or cultures, food or biological matrices making their extraction, analysis, and purification very challenging. The development of efficient analytical methods dedicated to lignans helps to provide new insight in the natural lignan chemodiversity, evolution throughout the plant kingdom as well as metabolization/detoxification following their absorption/injection in the human body. Moreover, although most in vivo and in vitro data are globally in favor of a chemopreventive effect of lignans, epidemiological studies are sometimes much less conclusive and the mechanism still remains unclear and requires further elucidation. Therefore, the availability of purified lignans at a reasonable cost would allow easier in vivo supplementation experiments and elucidation of mechanisms.

All the known in planta biosynthesis roles as well as health benefits of lignans provide new frontiers for scientists from diverse fields of expertise to further study, elucidate or establish biosynthetic pathways, metabolic engineering, analytical methods and health action mechanisms of this important class of phytochemicals.

This Research Topic is devoted to the latest new insights, in the form of Reviews and Original Research articles, as well as Communication and Perspective papers covering several aspects of plant lignans including:

1) Biosynthesis: gene expression regulation, gene identification, enzyme characterization, chemical ecology, and pathway evolution, etc. Note that descriptive studies involving omics approaches with no functional insights into plant biology are not considered for review.

2) Phytochemistry/analytical methods: occurrence and diversity in plant lineage, extraction, separation and purification analytical methods, structural elucidation, etc. Note that only studies focusing on the plant standpoint will be considered.

3) Metabolic engineering: plants, in vitro cultures, elicitation, biotransformation, biocatalysts, etc.

4) Biological activity of lignans related to human health: in vitro and in vivo laboratory experiments, epidemiological studies, potential mechanisms and effects on human diseases, toxicology, potential side effects, etc. Note that studies carried out with crude extracts will not be considered for review. Only the use of highly purified, chemically characterized compounds is acceptable.

Keywords: Lignans, Metabolic engineering, Analytical methods, Biological activity, Lignans metabolism

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