RESUMO
Fungal meroterpenoids are important bioactive natural products. Their biosynthetic machineries are highly diverse, and reconstitutions lead to the production of unnatural meroterpenoids. In this study, heterologous gene expression in Aspergillus oryzae and in vitro assays elucidated the biosynthetic pathway of the orthoester-containing fungal meroterpenoid austalide F. Remarkably, the α-ketoglutarate-dependent oxygenase AstB produces the hemiacetal intermediate, and the methyltransferase AstL transfers a methyl group on it to construct the orthoester functionality. This study presents the extraordinary orthoester biosynthetic machinery and provides valuable insights into the creation of unnatural novel bioactive meroterpenoids through engineered biosynthesis. This article is part of the theme issue 'Reactivity and mechanism in chemical and synthetic biology'.
Assuntos
Aspergillus oryzae , Vias Biossintéticas , Terpenos , Terpenos/metabolismo , Aspergillus oryzae/metabolismo , Genes Fúngicos , Regulação Fúngica da Expressão GênicaRESUMO
BACKGROUND/AIM: In maintenance hemodialysis (MHD), protein-energy malnutrition and chronic inflammation can be critical and are two of the main causes of mortality. METHOD: We compared the change in nutrition and inflammatory conditions between younger and older MHD patients during a 2-year period. Furthermore, using Kaplan-Meier analysis, we evaluated the correlations between changes in each parameter and any adverse events. RESULT: During the observational period, body mass index (BMI) and serum albumin levels decreased significantly in older patients. In Kaplan-Meier analysis, patients who showed a decline in BMI had an associated elevated risk for cerebro-cardiovascular disease and hospitalization. Moreover, patients who showed a decline in albumin also had an associated higher risk for infectious disease and hospitalization. CONCLUSION: This study revealed that the downward trend in nutritional status was prominent in elderly patients. Furthermore, changes in nutritional and inflammatory conditions during MHD were associated with adverse events in MHD patients.