Dirigent proteins: molecular characteristics and potential biotechnological applications

  title={Dirigent proteins: molecular characteristics and potential biotechnological applications},
  author={Benjamin Pickel and Andreas Schaller},
  journal={Applied Microbiology and Biotechnology},
Dirigent proteins (DIRs) are thought to play important roles in plant secondary metabolism. They lack catalytic activity but direct the outcome of bimolecular coupling reactions toward regio- and stereospecific product formation. Functionally described DIRs confer specificity to the oxidative coupling of coniferyl alcohol resulting in the preferred production of either (+)- or (−)-pinoresinol, which are the first intermediates in the enantiocomplementary pathways for lignan biosynthesis. DIRs… 

Dirigent Proteins Guide Asymmetric Heterocoupling for the Synthesis of Complex Natural Product Analogues.

Phenylpropanoids are a class of abundant building blocks found in plants and derived from phenylalanine and tyrosine. Phenylpropanoid polymerization leads to the second most abundant biopolymer

Regio- and stereoselective intermolecular phenol coupling enzymes in secondary metabolite biosynthesis.

The discoveries reviewed in this article reveal a remarkable diversity of enzymes that catalyze oxidative intermolecular phenol coupling, including various classes of laccases, cytochrome P450 enzymes, and heme peroxidases.

Laccase-mediated synthesis of bioactive natural products and their analogues

This review summarizes selected examples from the last decade's literature about the laccase-mediated synthesis of biologically active natural products and their analogues, which will include lignans and neolignans, dimeric stilbenoids, biflavonoids, biaryls and other compounds of potential interest for the pharmaceutical industry.

Expression in Pichia pastoris and characterization of two novel dirigent proteins for atropselective formation of gossypol

We established an efficient fed-batch fermentation process for two novel dirigent proteins from cotton plants, GbDIR2 from Gossypium barbadense and GhDIR3 from G. hirsutum, using the engineered

Enzymatic dimerization in the biosynthetic pathway of microbial natural products.

This review focuses on the enzymes involved in the dimerization in the biosynthetic pathway of microbial natural products, with an emphasis on cytochrome P450s, laccases, and intermolecular [4 + 2] cyclases, along with other atypical enzymes.

Fungal Dirigent Protein Controls the Stereoselectivity of Multicopper Oxidase-Catalyzed Phenol Coupling in Viriditoxin Biosynthesis.

A unique Baeyer-Villiger monooxygenase (BVMO) VdtE that could transform the alkyl methylketone side chain to methyl ester against the migratory aptitude is uncovered.

Small Cells for Big Ideas: The Cytotoxic Podophyllotoxin and the Long Journey in Discovering Its Biosynthetic Pathway

Compelling discoveries and unexpected turns of the lignan biosynthetic pathway are discussed next, followed by benchmark studies in the aseptic cultivation of the plants producing it.

Dirigent Proteins from Cotton (Gossypium sp.) for the Atropselective Synthesis of Gossypol.

The identification of GhDIR4 highlights a broader role for DIRs in plant secondary metabolism and may eventually lead to the development of DIR's as tools for the synthesis of axially chiral binaphthyls.

The Missing Link in Leguminous Pterocarpan Biosynthesis is a Dirigent Domain-Containing Protein with Isoflavanol Dehydratase Activity

In suspension-cultured soybean cells, levels of the GmPTS1 transcript increased temporarily prior to the peak in phytoalexin accumulation, strongly supporting the possible involvement of PTS in pterocarpan biosynthesis.

Lignanamides: sources, biosynthesis and potential health benefits – a minireview

The general biosynthesis pathway for lignanamides is comprehensively summarized, though some details in molecular regulation of the coupling process have yet to be elucidated.



Optimized expression of the dirigent protein AtDIR6 in Pichia pastoris and impact of glycosylation on protein structure and function

It is demonstrated that the glycan structures of AtDIR6 are essential for structure, solubility, and function of the protein as deglycosylation induced conformational changes leading to the complete loss in dirigent activity and subsequent protein aggregation.

Regiochemical control of monolignol radical coupling: a new paradigm for lignin and lignan biosynthesis.

Evolution of the Chalcone Isomerase Fold from Fatty Acid-Binding to Stereospecific Enzyme

Specialized metabolic enzymes biosynthesize chemicals of ecological importance, often sharing a pedigree with primary metabolic enzymes. However, the lineage of the enzyme chalcone isomerase (CHI)

Molecular mechanism of enzymatic allene oxide cyclization in plants.

A model of dirigent proteins derived from structural and functional similarities with allene oxide cyclase and lipocalins

It is shown here that the dirigent protein AtDIR6 from Arabidopsis’thaliana is a homodimeric all‐beta protein in the superfamily of calycins, suggesting that dirigent proteins evolved from hydrophobic ligand‐binding proteins.

Kinetic study of coniferyl alcohol radical binding to the (+)-pinoresinol forming dirigent protein.

A mechanism of directed radical-radical coupling, where two coniferyl alcohol radical substrates are bound per protein dimer is proposed, which strongly suggest that CA(*, rather than CA, is the substrate for DP, in agreement with earlier predictions.

(+)-Pinoresinol/(+)-Lariciresinol Reductase from Forsythia intermedia

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Secondary and quaternary structures of the (+)-pinoresinol-forming dirigent protein.

Analytical ultracentrifugation, sedimentation velocity, and sedimentation equilibrium analyses of the native dirigent protein in open solution confirmed further its dimeric nature as well as a propensity to aggregate, with the latter being dependent upon both temperature and solution ionic strength.

Stilbene oligomers from Parthenocissus laetevirens: isolation, biomimetic synthesis, absolute configuration, and implication of antioxidative defense system in the plant.

The results showed that stilbene oligomers with an unusual phenanthrene moiety exhibited much stronger antioxidant activities, which was hypothesized to play a role in the antioxidative defense system of the plant.

Dirigent-mediated podophyllotoxin biosynthesis in Linum flavum and Podophyllum peltatum.