Antiviral Agents From Fungi: Diversity, Mechanisms and Potential Applications

Much of natural product chemistry concerns a group of compounds known as secondary metabolites. These low-molecular-weight metabolites often have potent physiological activities. Digitalis, morphine and quinine are plant secondary metabolites, whereas penicillin, cephalosporin, ergotrate and the statins are equally well known fungal secondary metabolites. Although chemically diverse, all secondary metabolites are produced by a few common biosynthetic pathways, often in conjunction with morphological development. Recent advances in molecular biology, bioinformatics and comparative genomics have revealed that the genes encoding specific fungal secondary metabolites are clustered and often located near telomeres. In this review, we address some important questions, including which evolutionary pressures led to gene clustering, why closely related species produce different profiles of secondary metabolites, and whether fungal genomics will accelerate the discovery of new pharmacologically active natural products.

Fungi produce a multitude of low-molecular-mass compounds known as secondary metabolites, which have roles in a range of cellular processes such as transcription, development and intercellular communication. In addition, many of these compounds now have important applications, for instance, as antibiotics or immunosuppressants. Genome mining efforts indicate that the capability of fungi to produce secondary metabolites has been substantially underestimated because many of the fungal secondary metabolite biosynthesis gene clusters are silent under standard cultivation conditions. In this Review, I describe our current understanding of the regulatory elements that modulate the transcription of genes involved in secondary metabolism. I also discuss how an improved knowledge of these regulatory elements will ultimately lead to a better understanding of the physiological and ecological functions of these important compounds and will pave the way for a novel avenue to drug discovery through targeted activation of silent gene clusters.

The question of how many species of Fungi there are has occasioned much speculation, with figures mostly posited from around half a million to 10 million, and in one extreme case even a sizable portion of the spectacular number of 1 trillion. Here we examine new evidence from various sources to derive an updated estimate of global fungal diversity. The rates and patterns in the description of new species from the 1750s show no sign of approaching an asymptote and even accelerated in the 2010s after the advent of molecular approaches to species delimitation. Species recognition studies of (semi-)cryptic species hidden in morpho-species complexes suggest a weighted average ratio of about an order of magnitude for the number of species recognized after and before such studies. New evidence also comes from extrapolations of plant:fungus ratios, with information now being generated from environmental sequence studies, including comparisons of molecular and fieldwork data from the same sites. We further draw attention to undescribed species awaiting discovery in biodiversity hot spots in the tropics, little-explored habitats (such as lichen-inhabiting fungi), and material in collections awaiting study. We conclude that the commonly cited estimate of 1.5 million species is conservative and that the actual range is properly estimated at 2.2 to 3.8 million. With 120,000 currently accepted species, it appears that at best just 8%, and in the worst case scenario just 3%, are named so far. Improved estimates hinge particularly on reliable statistical and phylogenetic approaches to analyze the rapidly increasing amount of environmental sequence data.