Artificial intelligence for natural product drug discovery.

Developments in computational omics technologies have provided new means to access the hidden diversity of natural products, unearthing new potential for drug discovery. In parallel, artificial intelligence approaches such as machine learning have led to exciting developments in the computational drug design field, facilitating biological activity prediction and de novo drug design for molecular targets of interest. Here, we describe current and future synergies between these developments to effectively identify drug candidates from the plethora of molecules produced by nature.

QTL mapping and genomic analyses of earliness and fruit ripening traits in a melon Recombinant Inbred Lines population supported by de novo assembly of their parental genomes.

Earliness and ripening behavior are important attributes of fruits on and off the vine, and affect quality and preference of both growers and consumers. Fruit ripening is a complex physiological process that involves metabolic shifts affecting fruit color, firmness, and aroma production. Melon is a promising model crop for the study of fruit ripening, as the full spectrum of climacteric behavior is represented across the natural variation.

Conserved noncoding sequences provide insights into regulatory sequence and loss of gene expression in maize.

Thousands of species will be sequenced in the next few years; however, understanding how their genomes work, without an unlimited budget, requires both molecular and novel evolutionary approaches. We developed a sensitive sequence alignment pipeline to identify conserved noncoding sequences (CNSs) in the Andropogoneae tribe (multiple crop species descended from a common ancestor ∼18 million years ago). The Andropogoneae share similar physiology while being tremendously genomically diverse, harboring a broad range of ploidy levels, structural variation, and transposons.

Comparison of irrigant activation devices and conventional needle irrigation on smear layer and debris removal in curved canals. (Smear layer removal from irrigant activation using SEM).

Aim: To compare the effectiveness of smear layer and debris removal in the final rinse of curved canals of permanent molars using different commercially available irrigant activation devices.

Methods: The mesial roots of 74 extracted maxillary and mandibular molars were instrumented using the Mtwo nickel-titanium rotary system (VDW GmbH, Munich, Germany). They were then randomly assigned to one of three groups, varying in their final rinse protocol.

Conserved bacterial genomes from two geographically isolated peritidal stromatolite formations shed light on potential functional guilds.

Stromatolites are complex microbial mats that form lithified layers. Fossilized stromatolites are the oldest evidence of cellular life on Earth, dating back over 3.4 billion years.

Horizontal Gene Transfer to a Defensive Symbiont with a Reduced Genome in a Multipartite Beetle Microbiome.

Symbiotic mutualisms of bacteria and animals are ubiquitous in nature, running a continuum from facultative to obligate from the perspectives of both partners. The loss of functions required for living independently but not within a host gives rise to reduced genomes in many symbionts. Although the phenomenon of genome reduction can be explained by existing evolutionary models, the initiation of the process is not well understood.

In situ mass spectrometry monitoring of fungal cultures led to the identification of four peptaibols with a rare threonine residue.

Peptaibols are an intriguing class of fungal metabolites due both to their wide range of reported bioactivities and to the structural variability that can be generated by the exchange of variable amino acid building blocks. In an effort to streamline the discovery of structurally diverse peptaibols, a mass spectrometry surface sampling technique was applied to screen the chemistry of fungal cultures in situ. Four previously undescribed peptaibols, all containing a rare threonine residue, were identified from a fungal culture (MSX53554), which was identified as Nectriopsis Maire (Bionectriaceae, Hypocreales, Ascomycota).

Spatial and Temporal Profiling of Griseofulvin Production in Xylaria cubensis Using Mass Spectrometry Mapping.

A large portion of natural products research revolves around the discovery of new, bioactive chemical entities; however, studies to probe the biological purpose of such secondary metabolites for the host organism are often limited. Mass spectrometry mapping of secondary metabolite biosynthesis in situ can be used to probe a series of ecological questions about fungi that may be lost through traditional natural products chemistry extraction protocols. A griseofulvin-producing fungal culture of the Xylariaceae family, isolated as an endophyte of the tree Asimina triloba, was analyzed through a series of spatial and temporal mapping experiments.