Comparative Analysis of the Extradiol Ring-Cleavage Dioxygenase LigB from Arabidopsis and 3,4-Dihydroxyphenylalanine Dioxygenase from Betalain-Producing Plants.

Diverse arrays of naturally occurring compounds in plants are synthesized by specialized metabolic enzymes, many of which are distributed taxonomically. Although anthocyanin pigments are widely distributed and ubiquitous, betalains have replaced anthocyanins in most families in Caryophyllales. Anthocyanins and betalains never occur together in the same plant. The formation of betalamic acid, catalyzed by 3,4-dihydroxyphenylalanine (DOPA) 4,5-extradiol dioxygenase (DOD), is a key step in betalain biosynthesis. DODs in betalain-producing plants are coded by LigB genes, homologs of which have been identified in a wide range of higher plant orders, as well as in certain fungi and bacteria. Two classes of LigB homologs have been reported: those found in anthocyanin-producing species and those found in betalain-producing species, which contain DOD. To gain insight into the evolution of specialized metabolic enzymes involved in betalain biosynthesis, we performed a comparative biochemical analysis of Arabidopsis LigB, an extradiol ring-cleavage dioxygenase in anthocyanin-producing Arabidopsis and Phytolacca DOD1 of betalain-producing Phytolacca americana. We show that Arabidopsis LigB catalyzes 2,3-extradiol cleavage of DOPA to synthesize muscaflavin, whereas Phytolacca DOD1 converts DOPA to betalamic acid via 4,5-extradiol cleavage. Arabidopsis LigB also converts caffeic acid, a ubiquitous phenolic compound in higher plants, to iso-arabidopic acid in vitro via 2,3-extradiol cleavage of the aromatic ring. Amino-acid substitution in Arabidopsis LigB and Phytolacca DOD1 led to variable extradiol ring-cleavage function, supporting the suggestion that catalytic promiscuity serves as a starting point for the divergence of new enzymatic activities.

Histopathological analysis of skin reactions after coronavirus disease 2019 vaccination: Increment in number of infiltrated plasmacytoid dendritic cell.

Skin disorders are frequent adverse events after coronavirus disease 2019 (COVID-19) vaccination. However, the pathogenesis of these disorders is not fully understood. Here, we report a case series of cutaneous adverse events following COVID-19 vaccination, and the results of our investigation reveal the underlying mechanism. Case 1: a 47-year-old female developed a wheal, confined to the COVID-19 vaccination site, 2 days after her first injection. She was treated with topical steroids and oral antihistamines. Case 2: a 51-year-old female showed generalized petechial erythema accompanied by fever, genital bleeding, thrombocytopenia, liver dysfunction, and disseminated intravascular coagulation, 2 days after her second injection. She was diagnosed with vaccine-induced macrophage activation syndrome and treated with anti-inflammatory therapy. Immunohistological analysis of the skin eruption, in both these cases, showed infiltration of CD123+ BDCA2+ plasmacytoid dendritic cells (p-DC). Despite the distinctive clinical features in these two cases, this finding suggests that p-DC might be involved in different cutaneous adverse events after COVID-19 vaccination.