Fungi contain a remarkable diversity of both primary and secondary metabolic pathways involved in ecologically specialized or accessory functions. Genes in these pathways are frequently physically linked on fungal chromosomes, forming metabolic gene clusters (MGCs). In this Review, we describe the diversity in the structure and content of fungal MGCs, their population-level and species-level variation, the evolutionary mechanisms that underlie their formation, maintenance and decay, and their ecological and evolutionary impact on fungal populations. We also discuss MGCs from other eukaryotes and the reasons for their preponderance in fungi. Improved knowledge of the evolutionary life cycle of MGCs will advance our understanding of the ecology of specialized metabolism and of the interplay between the lifestyle of an organism and genome architecture.

The birth, evolution and death of metabolic gene clusters in fungi

A translational synthetic biology platform for rapid access to gram-scale quantities of novel drug-like molecules.

Triterpenoid-biosynthetic UDP-glycosyltransferases from plants.

The ovarian system comprises vital organs in females and is of great significance for the maintenance of reproductive potential and endocrine stability. Although complex pathogenesis undoubtedly contributes to ovarian aging, increasing attention is being paid to the extensive influence of oxidative stress. However, the role of oxidative stress in ovarian aging is yet to be fully elucidated. Exploring oxidative stress-related processes might be a promising strategy against ovarian aging. In this review, compelling evidence is shown that oxidative stress plays a role in the etiology of ovarian aging and promotes the development of other ovarian aging-related etiologies, including telomere shortening, mitochondrial dysfunction, apoptosis, and inflammation. In addition, some natural antioxidants such as quercetin, resveratrol, and curcumin have a protective role in the ovaries through multiple mechanisms. These findings raise the prospect of oxidative stress modulator-natural antioxidants as therapeutic interventions for delaying ovarian aging.

/pdf/the-role-of-oxidative-stress-and-natural-antioxidants-in-5de270pxtx.pdf

The Role of Oxidative Stress and Natural Antioxidants in Ovarian Aging.

Phylotranscriptomics in Cucurbitaceae Reveal Multiple Whole-Genome Duplications and Key Morphological and Molecular Innovations.

The consumption of sweeteners, natural as well as synthetic sugars, is implicated in an array of modern-day health problems. Therefore, natural nonsugar sweeteners are of increasing interest. We identify here the biosynthetic pathway of the sweet triterpenoid glycoside mogroside V, which has a sweetening strength of 250 times that of sucrose and is derived from mature fruit of luo-han-guo (Siraitia grosvenorii, monk fruit). A whole-genome sequencing of Siraitia, leading to a preliminary draft of the genome, was combined with an extensive transcriptomic analysis of developing fruit. A functional expression survey of nearly 200 candidate genes identified the members of the five enzyme families responsible for the synthesis of mogroside V: squalene epoxidases, triterpenoid synthases, epoxide hydrolases, cytochrome P450s, and UDP-glucosyltransferases. Protein modeling and docking studies corroborated the experimentally proven functional enzyme activities and indicated the order of the metabolic steps in the pathway. A comparison of the genomic organization and expression patterns of these Siraitia genes with the orthologs of other Cucurbitaceae implicates a strikingly coordinated expression of the pathway in the evolution of this species-specific and valuable metabolic pathway. The genomic organization of the pathway genes, syntenously preserved among the Cucurbitaceae, indicates, on the other hand, that gene clustering cannot account for this novel secondary metabolic pathway.

https://www.pnas.org/content/pnas/113/47/E7619.full.pdf

The biosynthetic pathway of the nonsugar, high-intensity sweetener mogroside V from Siraitia grosvenorii.

Hyoscyamine, anisodamine
and scopolamine are tropane alkaloids present
in some Solanaceae species and used in modern medicine. L-Hyoscyamine is hydroxylated
to 6β-hydroxyhyoscyamine
(anisodamine) and then epoxidated to scopolamine
by the dual action of hyoscyamine 6β-hydroxylase
(H6H), a 2-oxoglutarate dependent dioxygenase.
A natural mutation in the Gly-220 residue to Cys was previously shown to be associated
with the loss of function of H6H in Mandragora officinarum, preventing
the accumulation of anisodamine and scopolamine in these plants. We show here
that a deliberate Gly220Cys mutation in the Datura innoxia DiH6H protein caused a loss of both its enzymatic abilities
and rendered it unable to hydroxylate L-hyoscyamine into anisodamine and to epoxidate anisodamine into scopolamine. By using protein modeling
based on an available crystal structure of H6H from Datura metel, we show how the Cys220 residue causes
a steric interference in the active site cavity impairing the interaction of both
substrates, hyoscyamine and anisodamine with the active site of the protein. We also address the enantiomeric
preference of DiH6H based on molecular modeling.

/pdf/further-insights-on-the-datura-innoxia-hyoscyamine-6b-es7i01dqrf.pdf

Further Insights on the Datura innoxia Hyoscyamine 6β-Hydroxylase (DiH6H) Based on Biochemical Characterization and Molecular Modeling

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The biosynthetic pathway of the nonsugar, high-intensity sweetener mogroside V from Siraitia grosvenorii.

Further Insights on the Datura innoxia Hyoscyamine 6β-Hydroxylase (DiH6H) Based on Biochemical Characterization and Molecular Modeling