A5048574986- Trypanosoma species research and implications
- Research on Leishmaniasis Studies
- Helminth infection and control
- Microbial Natural Products and Biosynthesis
- Animal Behavior and Reproduction
- Insect and Arachnid Ecology and Behavior
- Polyamine Metabolism and Applications
- Cyclopropane Reaction Mechanisms
- Malaria Research and Control
- Biochemical and Molecular Research
- Bipolar Disorder and Treatment
- Genetics, Aging, and Longevity in Model Organisms
- Metalloenzymes and iron-sulfur proteins
- Mitochondrial Function and Pathology
- Sulfur Compounds in Biology
- Genomics and Phylogenetic Studies
- Synthesis and Catalytic Reactions
- Ammonia Synthesis and Nitrogen Reduction
- Microbial Community Ecology and Physiology
- Bacterial Genetics and Biotechnology
- ATP Synthase and ATPases Research
- Catalytic C–H Functionalization Methods
Harvard University
2014-2022
N-Nitroso-containing natural products are bioactive metabolites with antibacterial and anticancer properties. In particular, compounds containing the diazeniumdiolate (N-nitrosohydroxylamine) group display a wide range of bioactivities ranging from cytotoxicity to metal chelation. Despite importance this structural motif, knowledge its biosynthesis is limited. Herein we describe discovery biosynthetic gene cluster in Streptomyces alanosinicus ATCC 15710 responsible for producing product...
Diazo groups are found in a range of natural products that possess potent biological activities. Despite longstanding interest these metabolites, diazo group biosynthesis is not well understood, part because difficulties identifying specific genes linked to formation. Here we describe the discovery gene cluster produces o-diazoquinone product cremeomycin and its heterologous expression Streptomyces lividans. We used stable isotope feeding experiments vitro characterization biosynthetic...
The mechanisms underlying resistance of the Chagas disease parasite, Trypanosoma cruzi, to current therapies are not well understood, including role metabolic heterogeneity. We found that limiting exogenous glutamine protects actively dividing amastigotes from ergosterol biosynthesis inhibitors (azoles), independent parasite growth rate. antiparasitic properties azoles derived inhibition lanosterol 14α-demethylase (CYP51) in endogenous sterol synthesis pathway. find carbons 13C-glutamine...
Abstract Anopheles coluzzii females, important malaria vectors in Africa, mate only once their lifetime. Mating occurs aerial swarms with a high male-to-female ratio, where traits underlying male mating success are largely unknown. Here, we investigated whether cuticular hydrocarbons (CHCs) influence natural Burkina Faso. As insecticides widely used this area for control, also determined CHCs affect insecticide resistance levels. We find that mated males have higher CHC abundance than...
Desulfonation of isethionate by the bacterial glycyl radical enzyme (GRE) sulfite-lyase (IslA) generates sulfite, a substrate for respiration that in turn produces disease-associated metabolite hydrogen sulfide. Here, we present 2.7 Å resolution X-ray structure wild-type IslA from Bilophila wadsworthia with bound. In comparison other GREs, alternate positioning active site β strands allows distinct residue positions to contribute binding. These structural differences, combined sequence...
In addition to scavenging exogenous cholesterol, the parasitic kinetoplastid Trypanosoma cruzi can endogenously synthesize sterols. Similar fungal species, T. synthesizes ergostane type sterols and is sensitive a class of azole inhibitors ergosterol biosynthesis that target enzyme lanosterol 14α-demethylase (CYP51). related parasite Leishmania donovani, CYP51 essential, yet in major, cognate dispensable for growth; but not heat resistance. The essentiality specific role ergostane-type sterol...
Abstract N -nitroso-containing natural products are bioactive metabolites with antibacterial and anticancer properties. In particular, compounds containing the diazeniumdiolate ( -nitrosohydroxylamine) group display a wide range of bioactivities ranging from cytotoxicity to metal chelation. Despite importance this structural motif, knowledge its biosynthesis is limited. Herein, we describe discovery biosynthetic gene cluster in Streptomyces alanosinicus ATCC 15710 responsible for producing...
Abstract The mechanisms underlying resistance of the Chagas disease parasite, Trypanosoma cruzi, to current therapies are not well understood, including potential role metabolic heterogeneity in modulating susceptibility intracellular amastigotes trypanocidal compounds. We found that limiting exogenous glutamine protects actively dividing from ergosterol biosynthesis inhibitors (azoles), independent parasite growth rate. antiparasitic properties azoles derived inhibition lanosterol...
Abstract In addition to scavenging exogenous cholesterol, the parasitic kinetoplastid Trypanosoma cruzi can endogenously synthesize sterols. Similar fungal species, T. synthesizes ergostane type sterols and is sensitive a class of azole inhibitors ergosterol biosynthesis that target enzyme lanosterol 14α-demethylase (CYP51). related parasite Leishmania donovani , CYP51 essential, yet in major cognate dispensable for growth; but not heat resistance. The essentiality specific role...
Abstract Anopheles coluzzii females, important malaria vectors in Africa, mate only once their lifetime. Mating occurs aerial swarms with a high male-to-female ratio, where the traits underlying male mating success are largely unknown. Here, we investigated whether cuticular hydrocarbons (CHCs) influence natural Burkina Faso. As insecticides widely used this area for control, also determined CHCs affect insecticide resistance levels. We find that mated males have higher CHC abundance than...