Polycomb repressive complex 2 (PRC2) represents a group of evolutionarily conserved multi-subunit complexes that repress gene transcription by introducing trimethylation of lysine 27 on histone 3 (H3K27me3). PRC2 activity is of key importance for cell identity specification and developmental phase transitions in animals and plants. The composition, biochemistry, and developmental function of PRC2 in animal and flowering plant model species are relatively well described. Recent evidence demonstrates the presence of PRC2 complexes in various eukaryotic supergroups, suggesting conservation of the complex and its function. Here, we provide an overview of the current understanding of PRC2-mediated repression in different representatives of eukaryotic supergroups with a focus on the green lineage. By comparison of PRC2 in different eukaryotes, we highlight the possible common and diverged features suggesting evolutionary implications and outline emerging questions and directions for future research of polycomb repression and its evolution.

: The emergence of communicable and non-communicable diseases has posed a health challenge for millions of people worldwide and is a major threat to the economic and social development in the coming century. The occurrence of the recent pandemic, SARS-CoV-2, caused by lethal severe acute respiratory syndrome coronavirus 2, is one such example. Rapid research and development of drugs for the treatment and management of these diseases have become an incredibly challenging task for the pharmaceutical industry. Although, substantial attention has been paid to the discovery of therapeutic compounds from natural sources having significant medicinal potential, their synthesis has made a slow progress. Hence, the discovery of new targets by the application of the latest biotechnological and synthetic biology approaches is very much the need of the hour. Polyketides (PKs) and non-ribosomal peptides (NRPs) found in bacteria, fungi and plants are a diverse family of natural products synthesized by two classes of enzymes: polyketide synthases (PKS) and non-ribosomal peptide synthetases (NRPS). These enzymes possess immense biomedical potential due to their simple architecture, catalytic capacity, as well as diversity. With the advent of the latest in-silico and in-vitro strategies, these enzymes and their related metabolic pathways, if targeted, can contribute highly towards the biosynthesis of an array of potentially natural drug leads that have antagonist effects on biopolymers associated with various human diseases. In the face of the rising threat from multidrug-resistant pathogens, this will further open new avenues for the discovery of novel and improved drugs by combining natural and synthetic approaches. This review discusses the relevance of polyketides and non-ribosomal peptides and the improvement strategies for the development of their derivatives and scaffolds, and how they will be beneficial for future bioprospecting and drug discovery.

SUMMARY: The critically important YUCCA (YUC) gene family is highly conserved and specific to the plant kingdom, primarily responsible for the final and rate‐limiting step for indole‐3‐acetic acid (IAA) biosynthesis. IAA is an essential phytohormone, involved in virtually all aspects of plant growth and development. In addition, IAA is involved in fine‐tuning plant responses to biotic and abiotic interactions and stresses. While the YUC gene family has significantly expanded throughout the plant kingdom, a detailed analysis of the evolutionary patterns driving this diversification has not been performed. Here, we present a comprehensive phylogenetic analysis of the YUC family, combining YUCs from species representing key evolutionary plant lineages. The evolutionary history of YUCs is complex and suggests multiple recruitment events via horizontal gene transfer from bacteria. We identify and hierarchically classify the YUC family into an early diverging grade, five distinct classes and 41 subclasses. Angiosperm YUC diversity and expansion are explained in the context of protein sequence conservation, as well as spatial and gene expression patterns. The presented YUC gene landscape offers new perspectives on the distribution and evolutionary trends of this crucial family, which facilitates further YUC characterization within plant development and response to environmental change.

Quinolone synthase from Aegle marmelos (AmQNS) is a type III polyketide synthase that yields therapeutically effective quinolone and acridone compounds. Addressing the structural and molecular underpinnings of AmQNS and its substrate interaction in terms of its high selectivity and specificity can aid in the development of numerous novel compounds. This paper presents a high-resolution AmQNS crystal structure and explains its mechanistic role in synthetic selectivity. Additionally, we provide a model framework to comprehend structural constraints on ketide insertion and postulate that AmQNS’s steric and electrostatic selectivity plays a role in its ability to bind to various core substrates, resulting in its synthetic diversity. AmQNS prefers quinolone synthesis and can accommodate large substrates because of its wide active site entrance. However, our research suggests that acridone is exclusively synthesized in the presence of high malonyl-CoA concentrations. Potential implications of functionally relevant residue mutations were also investigated, which will assist in harnessing the benefits of mutations for targeted polyketide production. The pharmaceutical industry stands to gain from these findings as they expand the pool of potential drug candidates, and these methodologies can also be applied to additional promising enzymes.

To counteract pathogenic microorganisms, plants execute a complex resistance response that includes major metabolic reprogramming and production of bioactive defensive compounds. Barley ( Hordeum vulgare ) is a major cereal crop, but suffers significant yield losses due to pathogen attack every year. Here we use an untargeted metabolomic approach to assess the diversity and shifts in key barley metabolites produced in response to Pyrenophora teres f. teres infection, a hemibiotrophic fungal pathogen and causal agent of net blotch disease. Tryptophan-derived compounds, including tryptamine, serotonin, and a novel indole alkaloid – 2-oxo-tryptamine (2OT) – were among the most significantly induced and abundant compounds, with mass spectrometry imaging revealing that these metabolites accumulate at the site of infection. A transcriptomic approach identified a flavin-containing monooxygenase (FMO), which was functionally characterized as a 2-oxo-tryptamine synthase (2OTS). In addition, a cytochrome P450 (CYP71P10) was characterized as a tryptamine-5-hydroxylase, responsible for serotonin biosynthesis. These characterized genes are tightly co-expressed with genes involved in tryptophan biosynthesis and signify a major metabolic flux towards indolic compounds after infection, potentially serving as bioactive phytoalexins. Additional microbial interactions using a biotrophic fungus ( Blumeria hordei ; powdery mildew), a hemibiotrophic bacterium ( Pseudomonas syringae ), and alternative cultivars suggest that these pathways represent a generally activated resistance response in barley. These results provide new insights within the barley defense response relevant for the development of disease resistant traits in cereal crops.

The critically important YUCCA (YUC) gene family is highly conserved and specific to the plant kingdom, primarily responsible for the final and rate-limiting step for indole-3-acetic acid (IAA) biosynthesis. IAA is an essential phytohormone, involved in virtually all aspects of plant growth and development. In addition, IAA is involved in fine-tuning plant responses to biotic and abiotic interactions and stresses. While the YUC gene family has significantly expanded throughout the plant kingdom, a detailed analysis of the evolutionary patterns driving this diversification has not been performed. Here we present a comprehensive phylogenetic analysis of the YUC family, combining YUCs from species representing key evolutionary plant lineages. We identify and hierarchically classify the YUC family into six distinct classes and 41 subclasses. YUC diversity and expansion is explained in the context of protein sequence conservation, as well as spatial and gene expression patterns. The presented YUC gene landscape offers new perspectives on the distribution and evolutionary trends of this crucial family, which facilitates further YUC characterization within plant development and response to environmental change. Short summary Comprehensive phylogenetic and sequence analysis of the YUC gene family presents new insights into factors driving evolutionary diversification. Highlights A phylogeny-based classification system for the YUCCA gene family is presented YUCCA evolution and structural diversification is described, supporting a fine-tuned spatial and temporal control of auxin biosynthesis, but also holds potential for alternative capabilities