Biogenetic Origins Research Articles

Crepidamycins A-E, pyranonaphthoquinones from endophytic Streptomyces sp. MG-F-1 of Dendrobium crepidatum by the co-culture strategy.

On the basis of the co-culture strategy, five previously undescribed S-bridged pyranonaphthoquinones, crepidamycins A-E (1-5) and five known analogues (6-10) were isolated from a medicinal plant endophytic Streptomyces sp. MG-F-1 in Dendrobium crepidatum with Bacillus cereus MG-1. The structures and absolute configurations of 1-5 were elucidated by the interpretation of data from detailed spectroscopic analysis and electronic circular dichroism spectra, together with consideration of the biogenetic origins. Interestingly, these previously undescribed compounds were only found in the co-cultures and absent from the pure culture controls. Compounds 1-10 were assayed for their anti-inflammatory potential using LPS-stimulated RAW264.7 cells, of which compound 4 showed strong nitric oxide inhibitory effect with an IC50 of 0.22 ± 0.16 μM. The results of extracellular acidification rate and molecular docking suggest that it may play a role by regulating PKM2-mediated glycolysis.

A gene cluster encoding a nonribosomal peptide synthetase-like enzyme catalyzes γ-aromatic butenolides

Sea cucumber-derived fungi have attracted much attention due to their capacity to produce an incredible variety of secondary metabolites. Genome-wide information on Aspergillus micronesiensis H39 obtained using third-generation sequencing technology (PacBio-SMRT) showed that the strain contains nonribosomal peptide synthetase (NRPS)-like gene clusters, which aroused our interest in mining its secondary metabolites. 11 known compounds (1–11), including two γ-aromatic butenolides (γ-AB) and five cytochalasans, were isolated from A. micronesiensis H39. The structures of the compounds were determined by NMR and ESIMS, and comparison with those reported in the literature. From the perspective of biogenetic origins, the γ-butyrolactone core of compounds 1 and 2 was assembled by NRPS-like enzyme. All of the obtained compounds showed no inhibitory activity against drug-resistant bacteria and fungi, as well as compounds 1 and 2 had no anti-angiogenic activity against zebrafish.

Argenteolides A and B, Glycosylated Polyketide-Peptide Hybrid Macrolides from an Actinomycete Streptomyces argenteolus.

Two novel glycosylated polyketide-peptide hybrid macrolides, argenteolides A (1) and B (2), were isolated from an actinomycete Streptomyces argenteolus. Argenteolide A (1) contains a unique 5/5/5 tricyclic system in a 20-membered macrocycle. Their structures were elucidated by extensive spectroscopic analysis, and their stereochemical configurations were established through the application of chemical derivatization, J-based configuration analysis, DP4+ calculation, and electronic circular dichroism calculation. The analysis of the genome sequence revealed a plausible biosynthesis mechanism, and isotope-labeled feeding studies suggested their biogenetic origins. Argenteolides A and B exhibited moderate cytotoxicities against A549, p388, and Hela human carcinoma cell lines as well as antibacterial activities against Staphylococcus aureus and Escherichia coli ATCC25922.

Pro-angiogenic New Chloro-Azaphilone Derivatives From the Hadal Trench-Derived Fungus Chaetomium globosum YP-106.

Five new chloro-azaphilones, chaetofanixins A–E (1–5), and five known analogs (6–10) were isolated and identified from the hadal trench-derived fungus Chaetomium globosum YP-106. The structure of chaetofanixin E (5) is unique and interesting, bearing a highly rigid 6/6/5/3/5 penta-cyclic ring system, which is first encountered in natural products. The structures of these compounds, including absolute configurations, were determined based on the spectroscopic analysis, electronic circular dichroism (ECD) calculations, and analysis of biogenetic origins. Compounds 1–7 significantly promoted angiogenesis in a dose-dependent manner, and thus, these compounds might be used as promising molecules for the development of natural cardiovascular disease agents.

Extracellular Vesicle Proteomes Shed Light on the Evolutionary, Interactive, and Functional Divergence of Their Biogenesis Mechanisms.

Extracellular vesicles (EVs) are membranous structures containing bioactive molecules, secreted by most cells into the extracellular environment. EVs are classified by their biogenesis mechanisms into two major subtypes: ectosomes (enriched in large EVs; lEVs), budding directly from the plasma membrane, which is common in both prokaryotes and eukaryotes, and exosomes (enriched in small EVs; sEVs) generated through the multivesicular bodies via the endomembrane system, which is unique to eukaryotes. Even though recent proteomic analyses have identified key proteins associated with EV subtypes, there has been no systematic analysis, thus far, to support the general validity and utility of current EV subtype separation methods, still largely dependent on physical properties, such as vesicular size and sedimentation. Here, we classified human EV proteomic datasets into two main categories based on distinct centrifugation protocols commonly used for isolating sEV or lEV fractions. We found characteristic, evolutionarily conserved profiles of sEV and lEV proteins linked to their respective biogenetic origins. This may suggest that the evolutionary trajectory of vesicular proteins may result in a membership bias toward specific EV subtypes. Protein–protein interaction (PPI) network analysis showed that vesicular proteins formed distinct clusters with proteins in the same EV fraction, providing evidence for the existence of EV subtype-specific protein recruiters. Moreover, we identified functional modules enriched in each fraction, including multivesicular body sorting for sEV, and mitochondria cellular respiration for lEV proteins. Our analysis successfully captured novel features of EVs embedded in heterogeneous proteomics studies and suggests specific protein markers and signatures to be used as quality controllers in the isolation procedure for subtype-enriched EV fractions.

Secret Shame—Male Infertility and Donor Conception in the Wake of Retrospective Legislative Change

Historically, sperm donation was shrouded in secrecy to protect the normative family and the perceived vulnerability of infertile men. However, openness about donor conception is increasingly encouraged, in acknowledging that donor-conceived people may benefit from having access to information about their biogenetic origins. Since 2017 in the state of Victoria, Australia, donor-conceived people have been able to access previously anonymous donor records. Drawing on interviews with 17 donor-conceived adults who have come to know their donor through the new laws, this article explores the impact of finding out about the donor on relationships with mothers and fathers, and points to the persistent effects of stigma and shame about donor conception within families. Most of the donor-conceived participants were told about their donor conception in early adulthood. The age range for time of disclosure was mid-teens to early 40s. Most reported that their fathers did not want them to know. In some cases, mothers had disclosed, but sworn them to secrecy. Sensitivity to fathers’ feelings fostered a desire among participants to maintain secrecy about his infertility, especially in relation to wider family and friendship networks. Our findings revealed that secrecy about men’s infertility is heavily reliant on women’s emotional labor to protect ageing infertile fathers’ sense of manhood. Coupled with fathers’ overt resistance to openness, intergenerational secret keeping is perpetuated in families. Laws supporting openness potentially exacerbate the historical stigma associated with male factor infertility in a culture that continues to conflate virility, fertility, and masculinity.

Is Essentialism Essential? Reducing Homonegative Prejudice by Targeting Diverse Sexual Orientation Beliefs

We conducted an experiment to assess whether targeting multiple beliefs about sexual orientation (SO) may be more effective in reducing homonegativity than focusing only on beliefs about its biogenetic origins. Participants (116 women, 85 men) were randomly assigned to one of three treatment conditions or a control condition. Those in the treatment conditions read essays summarizing: (1) research suggesting SO has biogenetic origins, (2) research suggesting SO is socially constructed and refuting beliefs about the discreteness, homogeneity, and informativeness of SO categories; or (3) research suggesting SO is biogenetic and research suggesting SO categories are socially constructed and not necessarily discrete, homogenous, or informative. We predicted participants in the conditions that targeted multiple beliefs related to the social construction of SO, not just its biogenetic origins, would exhibit the strongest reductions in beliefs about the discreteness, homogeneity, and informativeness of SO categories, and in homonegativity. We also predicted these participants would exhibit the greatest increases in support for gay and lesbian civil rights. We observed hypothesized shifts in SO beliefs across all experimental conditions. While there was a small main effect of time on homonegative prejudice, there was no main effect of condition and no changes in support for gay and lesbian civil rights. However, post hoc analyses suggested the two conditions addressing social constructionist beliefs accounted for most of the observed prejudice reduction. Implications for more comprehensive educational and social interventions designed to promote social justice for sexual minorities are discussed.

Secondary Metabolites from Deep-Sea Derived Microorganisms.

Microorganisms obtained from the deep sea are a rich source of marine natural products with distinctive chemical structures and bioactivities. In this review, we will provide a retrospective of outstanding research within the scope of deep-sea (≥1000 m) microbial natural products, which has produced up to 442 compounds by the end of 2017. Approximetely, 60% of these structures have demonstrated various biological activities with more than 30% showing cytotoxic function. In this review, we particularly summarize those successful research on secondary metabolites produced by deep-sea derived microorganisms with inclusion of structural characteristics, biological activities, together with biogenetic origins and taxonomic features of the source microorganisms, from which, we expect to provide more comprehensive understanding of small molecules obtained from deep-sea environment and benefit the ongoing scholarly endeavors in the search for novel pharmaceutical agents from the deep-sea derived microorganisms.

Inducing Secondary Metabolite Production by Co-culture of the Endophytic Fungus Phoma sp. and the Symbiotic Fungus Armillaria sp.

Co-culturing the endophytic fungus Phoma sp. YUD17001 from Gastrodia elata with Armillaria sp. in liquid nutrient medium resulted in the production of five new secondary metabolites, including two phenolic compounds, phexandiols A and B (1 and 2), three aliphatic ester derivatives, phomesters A-C (3-5), and a known fatty acid (6). The structures and absolute configurations of these compounds were elucidated by the interpretation of data from detailed spectroscopic analysis, Mosher's method, and electronic circular dichroism spectra, together with consideration of the biogenetic origins. None of the five new compounds were detected in single-strain cultures under identical fermentation conditions. The results of this work indicated that the production of 1-5 involved a complicated interaction process. None of the new compounds possessed significant cytotoxicity or antimicrobial activities.

Aniline-Tetramic Acids from the Deep-Sea-Derived Fungus Cladosporium sphaerospermum L3P3 Cultured with the HDAC Inhibitor SAHA.

Four new tetramic acids, cladosins H-K (1-4), and a related known compound, cladodionen (5), were isolated from the culture of the Mariana Trench (depth 6562 m) sediment-derived fungus Cladosporium sphaerospermum L3P3 treated with the histone deacetylase inhibitor SAHA (suberanilohydroxamic acid). Interestingly, compounds 1-5 existed as equilibrium E/ Z mixtures and 1-4 were the first cases of tetramic acids containing aniline moieties. Their structures including absolute configurations were elucidated through a combination of NMR, MS, and Mosher's method, together with the consideration of biogenetic origins. Incubation experiments of exogenous aniline and N-phenyloctanamide revealed that the aniline moiety in cladosins H-K (1-4) is probably derived from the degradation of SAHA, indicating that the well-known histone deacetylase inhibitor SAHA could be metabolized by L3P3 and provide aniline as a precursor for biotransformation of chemically reactive polyketides. The cytotoxicity of 1-5 was evaluated against the PC-3, MGC-803, SH-SY5Y, HCT-116, K562, and HL-60 cell lines, and compound 2 showed promising cytotoxicity against the HL-60 cell line with an IC50 value of 2.8 μM.

Callyazepin and (3R)-Methylazacyclodecane, Nitrogenous Macrocycles from a Callyspongia sp. Sponge.

Callyazepin (1) and (3R)-methylazacyclodecane (2), nitrogenous macrocycles, were isolated from a tropical Callyspongia sp. sponge. The combined spectroscopic analyses revealed that the structure of 1 is a bicyclic azepane ammonium salt of a novel structural class derived from mixed biogenetic origins. The configuration of the whole molecule and the conformation of the formamide group were assigned by proton-proton coupling constants, a NOESY analysis, and the application of the phenylglycine methyl ester method. The structure of 2 was identified using combined spectroscopic analyses and ECD measurements. These compounds exhibited moderate cytotoxic activities against the K562 and A549 cell lines.

Biosynthetic Study of Amphidinin A and Amphidinolide P.

The biogenetic origins of amphidinin A (1) and amphidinolide P (2) were investigated by feeding experiments with (13)C-labeled acetates. (13)C-NMR data of (13)C-enriched samples revealed that the all carbons of 1 and 2 were derived from acetates. The polyketide chain of 1 was formed from one triketide chain, two diketide chains, and three unusual isolated C1 units derived from C-2 of cleaved acetates, while the polyketide chain of 2 was formed from one pentaketide chain, two acetate units, and three unusual isolated C1 units derived from C-2 of cleaved acetates. The all branched C1 units of 1 and 2 were derived from C-2 of cleaved acetates.

ChemInform Abstract: The Isolation and Synthesis of Neodolastane Diterpenoids

AbstractReview: 92 refs.

In vitro reconstitution of indolmycin biosynthesis reveals the molecular basis of oxazolinone assembly

The bacterial tryptophanyl-tRNA synthetase inhibitor indolmycin features a unique oxazolinone heterocycle whose biogenetic origins have remained obscure for over 50 years. Here we identify and characterize the indolmycin biosynthetic pathway, using systematic in vivo gene inactivation, in vitro biochemical assays, and total enzymatic synthesis. Our work reveals that a phenylacetate-CoA ligase-like enzyme Ind3 catalyzes an unusual ATP-dependent condensation of indolmycenic acid and dehydroarginine, driving oxazolinone ring assembly. We find that Ind6, which also has chaperone-like properties, acts as a gatekeeper to direct the outcome of this reaction. With Ind6 present, the normal pathway ensues. Without Ind6, the pathway derails to an unusual shunt product. Our work reveals the complete pathway for indolmycin formation and sets the stage for using genetic and chemoenzymatic methods to generate indolmycin derivatives as potential therapeutic agents.

Transition-metal and organocatalysis in natural product synthesis

The total synthesis of natural products, a field of organic chemistry that is both historical and contemporary, has undoubtedly entered a new paradigm over the past decade with the advent of revolutionary new synthetic methods and innovative synthetic concepts. Putting aside the downstream applications of natural-product synthesis in the interrogation of biological processes, elucidation of biogenetic origins, structural assignments and many others, its fundamental and indispensable value as a vehicle for the discovery of new synthetic transformations is well-testified and unparalleled by any other research discipline over the history of chemical science. These transformations, largely concerning carbon–carbon/carbon–heteroatom bond formations, asymmetric induction, and catalysis, constantly expand the repertoire of powerful tools available at the organic chemist’s disposal, and enable more challenging synthetic problems to be investigated. As such, this catalytic cycle of discovery fueled by natural-product synthesis continues to capture and captivate the imagination of both practitioners and students of organic chemistry around the world and will do so far beyond the foreseeable future. In particular, the recent discovery of novel transitional-metal complexes and their associated chemical transformations, and rediscovery of the unprecedented reactivity of previously documented transition-metal complexes with subtle changes in the reaction conditions and the reacting substrate have been extremely fruitful since the turn of the millennium, most notably in promoting reactions of unfunctionalized and unactivated chemical bonds. Furthermore, the application of organic compounds as promoters of chemical transformations has also witnessed increasing sophistication, substrate scope, and efficiency together with new modes of activation, which rival or at times surpass those exhibited by transition metals. Last but not least, the judiciary combination of transition-metal and organic mediators, together with tandem processes encompassing multiple reaction cycles in a programmed sequence, represents a new horizon with vast potentials that have yet to be fully understood and exploited.

Marine natural products

This review is a selection of the literature on marine natural products published in 2012. Natural products from a variety of marine sources with unusual structural features or interesting biological activities are highlighted. The compounds are organised loosely under their biogenetic origins of polyketides, terpenoids, meroterpenoids, alkaloids and peptides and miscellaneous natural products.

Considering the evidence and making the most empirically informed decision about depressive personality disorder in DSM-5.

In this paper, the criteria proposed by Kendler, Kupfer, Narrow, Philips, and Fawcett (2009) for the inclusion or exclusion of a diagnostic category in DSM-5 are reviewed as they relate to the proposal of depressive personality disorder (DPD). Three options are offered as possible decisions for the future of DPD, and a discussion of the actual decision by the Personality and Personality Disorders Work Group is provided. Despite what may ultimately be the removal of the DPD type from the DSM-5, it is concluded that there is considerable support for DPD as a diagnostic category. Such a conclusion incorporates most coherently the empirical findings about the DPD proposal in a way that allows for ongoing empirical investigation of its biogenetic origins, its phenotypic manifestations (including its trait profile) and possible characterization as an endophenotype, and the clinical utility it appears to hold among clinicians.

Marine natural products

This review covers the literature on marine natural products published in 2011. Natural products from a variety of marine sources with unusual structural features or interesting biological activities are highlighted. The compounds are organised loosely under their biogenetic origins of polyketides, terpenoids, meroterpenoids, alkaloids and peptides.

Marine natural products

This review covers the literature on marine natural products published in 2010. Natural products from a variety of marine sources with unusual structural features or interesting biological activities are highlighted. The compounds are organised loosely under their biogenetic origins of polyketides, terpenoids, alkaloids and peptides. In 2010 several marine natural products with with complex structures have been identified and biosynthetic pathways proposed for their formation.

The Trail Pheromone of a Stingless Bee, Trigona corvina (Hymenoptera, Apidae, Meliponini), Varies between Populations

Stingless bees, like honeybees, live in highly organized, perennial colonies. Their eusocial way of life, which includes division of labor, implies that only a fraction of the workers leave the nest to forage for food. To ensure a sufficient food supply for all colony members, stingless bees have evolved different mechanisms to recruit workers to foraging or even to communicate the location of particular food sites. In some species, foragers deposit pheromone marks between food sources and their nest, which are used by recruited workers to locate the food. To date, pheromone compounds have only been described for 3 species. We have identified the trail pheromone of a further species by means of chemical and electrophysiological analyses and with bioassays testing natural gland extracts and synthetic compounds. The pheromone is a blend of wax type and terpene esters. The relative proportions of the single components showed significant differences in the pheromones of foragers form 3 different colonies. This is the first report on a trail pheromone comprised of esters of 2 different biogenetic origins proving variability of the system. Pheromone specificity may serve to avoid confusions between the trails deposited by foragers of different nests and, thus, to decrease competition at food sources.