Phenolic amides (avenanthramides) in oats - an update review.

Oats (Avena sativa L.) are one of the worldwide cereal crops. Avenanthramides (AVNs), the unique plant alkaloids of secondary metabolites found in oats, are nutritionally important for humans and animals. Numerous bioactivities of AVNs have been investigated and demonstrated in vivo and in vitro. Despite all these, researchers from all over the world are taking efforts to learn more knowledge about AVNs. In this work, we highlighted the recent updated findings that have increased our understanding of AVNs bioactivity, distribution, and especially the AVNs biosynthesis. Since the limits content of AVNs in oats strictly hinders the demand, understanding the mechanisms underlying AVN biosynthesis is important not only for developing a renewable, sustainable, and environmentally friendly source in both plants and microorganisms but also for designing effective strategies for enhancing their production via induction and metabolic engineering. Future directions for improving AVN production in native producers and heterologous systems for food and feed use are also discussed. This summary will provide a broad view of these specific natural products from oats.

• Avenanthramides are unique nutritional alkaloids in oats• AVN bioactivity, distribution, and the potential AVNs biosynthesis are discussed• AVNs can be produced via induction and metabolic engineering.

Avenanthramides, Distinctive Hydroxycinnamoyl Conjugates of Oat, Avena sativa L.: An Update on the Biosynthesis, Chemistry, and Bioactivities.

Avenanthramides are a group of N-cinnamoylanthranilic acids (phenolic alkaloid compounds) that are produced in oat plants as phytoalexins, in response to pathogen attack and elicitation. The enzyme catalysing the cinnamamide-generating reaction is hydroxycinnamoyl-CoA: hydroxyanthranilate N-hydroxycinnamoyltransferase (HHT, a member of the super family of BAHD acyltransferases). HHT from oat appears to have a narrow range of substrate usage, with preferred use of 5-hydroxyanthranilic acid (and to a lesser extent, other hydroxylated and methoxylated derivatives) as acceptor molecules, but is able to use both substituted cinnamoyl-CoA and avenalumoyl-CoA thioesters as donor molecules. Avenanthramides thus combine carbon skeletons from both the stress-inducible shikimic acid and phenylpropanoid pathways. These features contribute to the chemical characteristics of avenanthramides as multifunctional plant defence compounds, as antimicrobial agents and anti-oxidants. Although avenanthramides are naturally and uniquely synthesised in oat plants, these molecules also exhibit medicinal and pharmaceutical uses important for human health, prompting research into utilisation of biotechnology to enhance agriculture and value-added production.

Exploiting Spermidine N-Hydroxycinnamoyltransferase Diversity and Substrate Promiscuity to Produce Various Trihydroxycinnamoyl Spermidines and Analogues in Engineered Yeast.

Trihydroxycinnamoyl spermidines (THCSpd) are plant specialized metabolites with promising pharmacological activities as antifungals, antibacterial, antiviral, and antidepressant drugs. However, their characterization and potential pharmaceutical exploitation are greatly impaired by the sourcing of these compounds, restricted to the pollen of core Eudicot plant species. In this work, we developed a precursor-directed biosynthesis of THCSpd in yeast using a dual enzymatic system based on 4-coumarate-CoA ligases (4CL) and spermidine N-hydroxycinnamoyltransferases (SHT). The system relies on the yeast endogenous spermidine pool and only requires hydroxycinnamic acids as exogenous precursors. By exploring 4CL isoforms and SHT diversity among plants, we have driven the production of 8 natural THCSpd, using single or mixed hydroxycinnamic acid precursors. Substrate promiscuities of 4CL and SHT were genuinely exploited to produce 8 new-to-nature THCSpd from exotic hydroxycinnamic and dihydrohydroxycinnamic acids, together with 3 new-to-nature THCSpd containing halogenated hydroxycinnamoyl moieties. In this work, we established a versatile and modular biotechnological production platform allowing the tailor-made THCSpd synthesis, constituting pioneer metabolic engineering for access to these valuable natural products.