What’s in Your Backyard?: A Curriculum Guide to Accompany The University of Oklahoma Citizen Science Soil Collection Program

This guide was designed to support educators by helping to integrate citizen science into the classroom environment. By including research about fungi in your classroom, you are helping to foster the development of scientific inquiry skills in students, while also contributing to cutting edge biomedical research being conducted at the University of Oklahoma.N

Practice Problems in Biomedical Organic Chemistry: Self-Guided Problems and Answers for Students in Bioorganic and Organic Chemistry, Volume I

If you have ideas for topics to be included in future volumes or have suggestion or corrections you would like to share, you can email the authors at [email protected] problem set was developed to assist undergraduate students taking a one semester or two semester, non-majors course in organic chemistry. Students in these courses often come to organic chemistry from diverse backgrounds including biology, microbiology, and a variety of medical-related fields (e.g., pre-medical, pre-nursing, pre-pharmacy, and others). If you are one of these students, these problems were made for you. We have generated a series of questions and answers dealing with major topics in organic chemistry as they apply to biology, medicine, and cell biology. In addition, we have included questions related to important analytical chemistry tools that students might encounter during their professional careers.University of Oklahoma Libraries Alternative Textbook GrantN

Terretonin, ophiobolin, and drimane terpenes with absolute configurations from an algicolous Aspergillus ustus

One new meroterpene, 1,2-dihydroterretonin F (2), five new sesterterpenes, (6a)-21-deoxyophiobolin G(3), (6a)-16,17-dihydro-21-deoxyophiobolin G (4), phiobolin U (5), ophiobolin V (6), and ophiobolin W (7),two new sesquiterpenes, (6-strobilactone-B) esters of (E,E)-6,7-epoxy-2,4-octadienoic acids (13 and 14),and twelve known terpenes (1, 8–12, and 15–20) were isolated from Aspergillus ustus, a fungus from the fresh tissue of marine green alga Codium fragile. Their structures and absolute configurations were identified by NMR and mass spectroscopic methods as well as quantum chemical calculations. Some of the isolates exhibited antibacterial activity and brine shrimp toxicity.One new meroterpene, 1,2-dihydroterretonin F (2), five new sesterterpenes, (6 alpha)-21-deoxyophiobolin G (3), (6 alpha)-16,17-dihydro-21-deoxyophiobolin G (4), ophiobolin U (5), ophiobolin V (6), and ophiobolin W(7), two new sesquiterpenes, (6-strobilactone-B) esters of (E,E)-6,7-epoxy-2,4-octadienoic acids (13 and 14), and twelve known terpenes (1, 8-12, and 15-20) were isolated from Aspergillus ustus, a fungus from the fresh tissue of marine green alga Codium fragile. Their structures and absolute configurations were identified by NMR and mass spectroscopic methods as well as quantum chemical calculations. Some of the isolates exhibited antibacterial activity and brine shrimp toxicity

Enhancement of transdermal fentanyl and buprenorphine antinociception by transdermal Δ 9 -tetrahydrocannabinol

Abstract Previous studies have demonstrated that Δ 9 -tetrahydrocannabinol (THC) enhances the antinociceptive potency of many opioids administered by a variety of different routes of administration. We hypothesized that THC would enhance fentanyl or buprenorphine analgesia via the transdermal route of administration. THC was first demonstrated to enhance opioid antinociception when both drugs were administered parenterally in a hairless guinea pig model using the pin prick test. A low dose of THC (50 mg/kg, i.p.) produced no antinociception. However, THC enhanced the potency of s.c. fentanyl by 6.7-fold, and s.c. buprenorphine in a non-parallel fashion. For the transdermal studies, THC, fentanyl or buprenorphine was applied by pipette to the skin of the dorsum between the fore-and hind-flanks and covered with individual Tegederm™ patches. THC (400 mg/kg) produced no antinociception. However, THC enhanced fentanyl's potency by 3.7-fold at 2-h, and 5.8-fold at 4-h. Buprenophine's potency was increased 8.2-fold at 2-h and 7.2-fold at 4-h when co-administered with THC. These results indicate that the enhancement of transdermal opioids by THC could lead to the design of an effective combination analgesic patch

Secondary Metabolites from an Algicolous Aspergillus versicolor Strain

Two new compounds, asperversin A (1) and 9ξ-O-2(2,3-dimethylbut-3-enyl)brevianamide Q (2), and nine known compounds, brevianamide K (3), brevianamide M (4), aversin (5), 6,8-di-O-methylnidurufin (6), 6,8-di-O-methylaverufin (7), 6-O-methylaverufin (8), 5α,8α-epidioxyergosta-6,22-dien-3β-ol (9), ergosta-7,22-diene-3β,5α,6β-triol (10), and 6β-methoxyergosta-7,22-diene-3β,5α-diol (11), were obtained from the culture of Aspergillus versicolor, an endophytic fungus isolated from the marine brown alga Sargassum thunbergii. The structures of these compounds were established by spectroscopic techniques. Compounds 4, 7 and 8 exhibited antibacterial activities against Escherichia coli and Staphyloccocus aureus, and 7 also showed lethality against brine shrimp (Artemia salina) with an LC50 value of 0.5 μg/mL

Impact of the cultivation strategy on resveratrol production from glucose in engineered Corynebacterium glutamicum

The health benefits of polyphenols such as stilbenes and flavonoids for humans are increasingly attracting attention. Resveratrol is awell-characterized naturally-occurring stilbeneandpotentanti-oxidant, which isused as food supplement and cosmetic ingredient. Several microorganisms including Corynebacterium glutamicum were engineered for resveratrol production from glucose. Based on the cultivation of a resveratrol-producing C. glutamicum strain in shake flasks, different strategies for improving production under controlled conditions at bioreactor scale were tested. To this end, different cultivation parameters including substrate concentration and operation modes (batch and fed-batch) were evaluated. Whereas the highest biomass concentration was observed during fed-batch fermentation, the maximum resveratrol production was achieved in batch mode. The maximal titer obtained was 12 mg L−1 of resveratrol without the addition of the fatty acid synthase inhibitor cerulenin, which was previously shown to be crucial for production with C. glutamicum. The specific growth rate duringproductionseemstohaveasignificanteffectinresveratrolproductionandapparentlylowspecificgrowth rates may redirect the metabolic bottleneck from p-coumaric acid formation to malonyl-CoA or ATP availability. We also show that high oxygen concentrations in the bioreactor negatively affected the obtained resveratrol titerswithC.glutamicum,whichismost likelydueto thestrongtendency ofresveratrol tooxidizeoroligomerize. Thus, up-scaling of the resveratrol production process is technically challenging and individual process parameters have to be optimized cautiously.We would like to thank the European Union Framework Program 7 "BacHBerry" (www.bachberry.eu), Project No. FP7- 613793 for financial support, the PortugueseFoundation forScience andTechnology (FCT) under the scope of the strategic funding of UID/BIO/04469/2013 unit, COMPETE 2020 (POCI-01-0145-FEDER-006684) and BioTecNorte operation (NORTE-01-0145-FEDER-000004) funded by the European Regional Development Fund under the scope of Norte2020 − Programa Operacional Regional do Norte.info:eu-repo/semantics/publishedVersio

Building Natural Product Libraries Using Quantitative Clade-Based and Chemical Clustering Strategies

The success of natural product-based drug discovery is predicated on having chemical collections that offer broad coverage of metabolite diversity. We propose a simple set of tools combining genetic barcoding and metabolomics to help investigators build natural product libraries aimed at achieving predetermined levels of chemical coverage. It was found that such tools aided in identifying overlooked pockets of chemical diversity within taxa, which could be useful for refocusing collection strategies. We have used fungal isolates identified as Alternaria from a citizen-science-based soil collection to demonstrate the application of these tools for assessing and carrying out predictive measurements of chemical diversity in a natural product collection. Within Alternaria, different subclades were found to contain nonequivalent levels of chemical diversity. It was also determined that a surprisingly modest number of isolates (195 isolates) was sufficient to afford nearly 99% of Alternaria chemical features in the data set. However, this result must be considered in the context that 17.9% of chemical features appeared in single isolates, suggesting that fungi like Alternaria might be engaged in an ongoing process of actively exploring nature’s metabolic landscape. Our results demonstrate that combining modest investments in securing internal transcribed spacer (ITS)-based sequence information (i.e., establishing gene-based clades) with data from liquid chromatography-mass spectrometry (i.e., generating feature accumulation curves) offers a useful route to obtaining actionable insights into chemical diversity coverage trends in a natural product library. It is anticipated that these outcomes could be used to improve opportunities for accessing bioactive molecules that serve as the cornerstone of natural product-based drug discovery.Open Access fees paid for in whole or in part by the University of Oklahoma Libraries.Ye

Discovery of platelet-type 12-human lipoxygenase selective inhibitors by high-throughput screening of structurally diverse libraries.

Human lipoxygenases (hLO) have been implicated in a variety of diseases and cancers and each hLO isozyme appears to have distinct roles in cellular biology. This fact emphasizes the need for discovering selective hLO inhibitors for both understanding the role of specific lipoxygenases in the cell and developing pharmaceutical therapeutics. To this end, we have modified a known lipoxygenase assay for high-throughput (HTP) screening of both the National Cancer Institute (NCI) and the UC Santa Cruz marine extract library (UCSC-MEL) in search of platelet-type 12-hLO (12-hLO) selective inhibitors. The HTP screen led to the characterization of five novel 12-hLO inhibitors from the NCI repository. One is the potent but non-selective michellamine B, a natural product, anti-viral agent. The other four compounds were selective inhibitors against 12-hLO, with three being synthetic compounds and one being alpha-mangostin, a natural product, caspase-3 pathway inhibitor. In addition, a selective inhibitor was isolated from the UCSC-MEL (neodysidenin), which has a unique chemical scaffold for a hLO inhibitor. Due to the unique structure of neodysidenin, steady-state inhibition kinetics were performed and its mode of inhibition against 12-hLO was determined to be competitive (K(i)=17microM) and selective over reticulocyte 15-hLO-1 (K(i) 15-hLO-1/12-hLO\u3e30)

Local Phenomena Shape Backyard Soil Metabolite Composition

Soil covers most of Earth’s continental surface and is fundamental to life-sustaining processes such as agriculture. Given its rich biodiversity, soil is also a major source for natural product drug discovery from soil microorganisms. However, the study of the soil small molecule profile has been challenging due to the complexity and heterogeneity of this matrix. In this study, we implemented high-resolution liquid chromatography–tandem mass spectrometry and large-scale data analysis tools such as molecular networking to characterize the relative contributions of city, state and regional processes on backyard soil metabolite composition, in 188 soil samples collected from 14 USA States, representing five USA climate regions. We observed that region, state and city of collection all influence the overall soil metabolite profile. However, many metabolites were only detected in unique sites, indicating that uniquely local phenomena also influence the backyard soil environment, with both human-derived and naturally-produced (plant-derived, microbially-derived) metabolites identified. Overall, these findings are helping to define the processes that shape the backyard soil metabolite composition, while also highlighting the need for expanded metabolomic studies of this complex environment.This research was supported by start-up funds from the University of Oklahoma (to L.-I.M.). Open Access fees paid for in whole or in part by the University of Oklahoma Libraries.Ye