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Efficient and selective biosynthesis of a precursor-directed FK506 analogue
Get PDFThe medically important immunosuppressant FK506 is a structurally complex macrolactone biosynthesized by a combined polyketide synthase and a nonribosomal peptide synthetase enzyme complex. Its acyltransferase domain 4 (AT4) selects an unusual extender unit, resulting in an allyl moiety on carbon 21 of the macrolactone backbone. Based on the AT4 domain, chemobiosynthetic processes have been developed that enable the introduction of diverse moieties at the carbon 21 position. However, the novel moieties that were introduced into the polyketide backbone are chemically inert. Reported here is a novel and efficient chemobiosynthetic approach that ensures high titer of an FK506 analogue containing a propargyl moiety. The novel FK506 analogue displays lower immunosuppression activity than FK506 with significantly reduced cytotoxicity. More importantly, the propargyl moiety contains a terminal alkyl group, which makes click chemistry reactions possiblethis approach may potentially be translated to other medically important drugs of polyketide origin
Napoved in raziskava razvoja dinamične rekristalizacije hadfieldskega jekla za jedra kretnic na železniških tirih
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Identification of potential human targets for epigallocatechin gallate through a novel protein binding site screening approach
Get PDFBiorefinery potential of low-value scots pine (Pinus sylvestris L.) and black locust (Robinia pseudoacacia L.) wood for the extraction of natural bioactive compounds for wood preservation
Get PDFS prispevkom želimo predstaviti glavne rezultate in povzetek znanstvenih dognanj, do katerih smo prišli z dvema nacionalnima podoktorskima projektoma ob podpori takratnega Ministrstva za izobraževanje, znanost in šport Republike Slovenije (MIZŠ) ter Javne agencije za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije (ARIS). Analizirali smo biorafinerijski potencial manjvrednega lesa rdečega bora (Pinus sylvestris L.) in robinije (Robinia pseudoacacia L.) za ekstrakcijo naravnih bioaktivnih spojin. Les grč in jedrovine smo uporabili kot biomaso za ekstrakcijo polifenolnih ekstraktivov, ki smo jih nato uporabili v naravno osnovanih pripravkih za zaščito lesa. Rezultati so pokazali, da hidrofilni ekstraktivi grč bora in jedrovine robinije zavirajo glivni razkroj lesa in imajo velik potencial kot biocidne komponente in antioksidanti v naravno osnovanih zaščitnih pripravkih. Nadaljnje raziskave antioksidativnih in protiglivnih lastnosti ekstraktivov lesa in skorje so v teku.This article presents the key results and scientific findings from two national postdoctoral research projects supported by the Ministry of Education, Science and Sport of the Republic of Slovenia (MIZŠ) and the Slovenian Research and Innovation Agency (ARIS). We analyzed the biorefinery potential of low-value Scots pine (Pinus sylvestris L.) and black locust (Robinia pseudoacacia L.) wood for the extraction of natural bioactive compounds. Knotwood and heartwood were used as biomass for extracting polyphenolic compounds, which were subsequently applied in bio-based wood preservatives. The results showed that hydrophilic extractives from Scots pine knotwood and black locust heartwood inhibit fungal decay and demonstrate strong potential as biocidal components and antioxidants in natural wood protection formulations. Further research on the antioxidant and antifungal properties of wood and bark extractives is ongoing