Search

Comparison of biosynthetic gene clusters (BGCs) found in devastating plant pathogens and biocontrol fungi revealed an uncharacterized and conserved polyketide BGC. Genome mining identified the associated metabolite to be treconorin, which has a terpene-like, trans-fused 5,7-bicyclic core that is proposed to derive from a (4 + 3) cycloaddition. The core is esterified with d-glucose, which derives from the glycosidic cleavage of a trehalose ester precursor. This glycomodification strategy is different from the commonly observed glycosylation of natural products.

We report biosynthetic pathways that can synthesize and transform conjugated octaenes and nonaenes to complex natural products. The biosynthesis of (-)-PF1018 involves an enzyme PfB that can control the regio-, stereo-, and periselectivity of multiple reactions starting from a conjugated octaene. Using PfB as a lead, we discovered a homologous enzyme, BruB, that facilitates diene isomerization, tandem 8π-6π-electrocyclization, and a 1,2-divinylcyclobutane Cope rearrangement to generate a new-to-nature compound.

Genome mining of biosynthetic pathways with no identifiable core enzymes can lead to discovery of the so-called unknown (biosynthetic route)-unknown (molecular structure) natural products. Here we focused on a conserved fungal biosynthetic pathway that lacks a canonical core enzyme and used heterologous expression to identify the associated natural product, a highly modified cyclo-arginine-tyrosine dipeptide. Biochemical characterization of the pathway led to identification of a new arginine-containing cyclodipeptide synthase (RCDPS), which was previously annotated as a hypothetical protein and has no sequence homology to non-ribosomal peptide synthetase or bacterial cyclodipeptide synthase. RCDPS homologs are widely encoded in fungal genomes; other members of this family can synthesize diverse cyclo-arginine-Xaa dipeptides, and characterization of a cyclo-arginine-tryptophan RCDPS showed that the enzyme is aminoacyl-tRNA dependent. Further characterization of the biosynthetic pathway led to discovery of new compounds whose structures would not have been predicted without knowledge of RCDPS function.

Seven new phloroglucinol derivatives, myrtucommunins A–D ( 1 – 4 ), 6-methylisomyrtucommulone B ( 5 ), 4-methylmyrtucommulone B ( 6 ), and 2-isobutyryl-4-methylphloroglucinol 1- O -β- d -glucopyranoside ( 7 ), and one new chromone derivative, undulatoside A 6′- O -gallate ( 8 ), were isolated from the leaves of Myrtus communis (Myrtaceae). Myrtucommunins A–D ( 1 – 4 ) were conjugates of polymethylated acylphloroglucinol and flavonol rhamnoside. The absolute configurations of the rhamnosyl moieties for 1 – 4 were confirmed to be l in each case by HPLC analyses, while those of the aglycones were assigned by comparisons of the experimental and TDDFT calculated ECD spectra. 6-Methylisomyrtucommulone B ( 5 ) and 4-methylmyrtucommulone B ( 6 ) were assigned as 6/6/6 tricyclic acylphloroglucinol derivatives with a racemic nature. Antimicrobial activities of 1 – 8 and related known compounds were evaluated. [ABSTRACT FROM AUTHOR]

A high incidence of endometrial adenocarcinoma and pre-neoplastic lesions was induced in ICR mice treated with N-methyl- N-nitrosourea and 17 β-oestradiol within 23 weeks. The endometrial lesions were histopathologically similar to those of human subjects. To assess the cell proliferative activity of these lesions, a one-step silver colloid staining for nucleolar organizer regions was applied and the numbers of silver-stained nucleolar organizer regions (AgNORs) were counted. The mean numbers±SD of AgNORs in each lesion were as follows: simple hyperplasia, 2.07±0.36; complex hyperplasia without cytological atypia, 2.79±0.39; complex hyperplasia with cytological atypia, 3.43±0.38; and well-differentiated adenocarcinoma, 4.17±0.40. Significant differences were observed in each lesion ( P<0.001). These findings suggest that the mean numbers of AgNORs are increased in the progression of neoplastic changes in the mouse endometrium, as in human endometrial lesions. This rapid induction model of endometrial carcinoma in mice is useful in the understanding of the histogenesis of endometrial carcinoma in human subjects. [ABSTRACT FROM AUTHOR]

Structurally unique C 28 terpenoids, perovsfolins A ( 1 ) and B ( 2 ), were isolated from the aerial parts of an Uzbek medicinal plant, Perovskia scrophulariifolia (Lamiaceae). Their chemical structures including an unprecedented 6/8/6/6/6 pentacyclic carbon skeleton with a C 6 -C 3 ester moiety were elucidated on the basis of spectroscopic analyses aided by density functional theory calculations as well as chemical evidence. Perovsfolin B ( 2 ) exhibited an anti-neuroinflammatory activity.