ABSTRACT
Two homologous meroterpenoid gene clusters consisting of contiguous genes encoding polyketide synthase (PKS), prenyltransferase (PT), terpenoid cyclase (TC) and other tailoring enzymes were identified from two phylogenetically distinct fungi through computational analysis. Media optimization guided by reverse-transcription PCR (RT-PCR) enabled two strains to produce eight new and two known meroterpenoids (1-10). Using gene inactivation, heterologous expression, and biochemical analyses, we revealed a new polyketide-terpenoid assembly line that utilizes a pair of PKSs to synthesize 2,4-dihydroxy-6-alkylbenzoic acid, followed by oxidative decarboxylation, farnesyl transfer, and terpene cyclization to construct the meroterpenoid scaffold. In addition, two of the isolated meroterpenoids (3 and 17 d) showed immunosuppressive bioactivity. Our work reveals a new strategy for meroterpenoid natural products discovery, and reveals the biosynthetic pathway for compounds 1-10.
Subject(s)
Fungi/genetics , Genome, Fungal , Terpenes/metabolism , Biological Products/chemistry , Biological Products/metabolism , Computational Biology , Cyclization , Dimethylallyltranstransferase/genetics , Dimethylallyltranstransferase/metabolism , Fungi/classification , Multigene Family , Phylogeny , Polyketide Synthases/genetics , Polyketide Synthases/metabolism , Terpenes/chemistryABSTRACT
Chaetospirolactone (1), a novel spiro-lactone bearing a rare 1-oxaspiro [4.4] non-7-ene-2,6-dione skeleton, and orsellide F (2), together with six known compounds (3-8), were isolated from an endophytic fungus Chaetomium sp. NF00754. Their structures were determined by interpretation of spectroscopic data. The absolute configurations of 1 and 2 were established by analysis of single X-ray crystallographic data and CD spectra. Compounds 3, 4, and 6 showed moderate acetylcholinesterase inhibitory activity with IC50 values of 7.34, 5.19, and 7.67 µM, respectively.
Subject(s)
Chaetomium/chemistry , Cholinesterase Inhibitors/isolation & purification , Cholinesterase Inhibitors/pharmacology , Lactones/isolation & purification , Resorcinols/isolation & purification , Spiro Compounds/isolation & purification , Acetylcholinesterase/drug effects , Cholinesterase Inhibitors/chemistry , Crystallography, X-Ray , Lactones/chemistry , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Resorcinols/chemistry , Spiro Compounds/chemistryABSTRACT
OBJECTIVE: To understand the knowledge and practice on schistosomiasis control of boatmen along the Yangtze River, so as to provide the evidence for making up schistosomiasis control measures for them. METHODS: In the anchor spots along the Yangtze River in Xinbei District, Changzhou City, a questionnaire survey was carried out for boatmen's knowledge and practice on schistosomiasis control. Among the boatmen of different genders, ages and education levels, the awareness rates of schistosomiasis control knowledge and the formation rates of correct behavior were compared. RESULTS: A total of 702 boatmen of 231 boats were surveyed. The total awareness rate of schistosomiasis control knowledge was 84.19%. Among the groups with different education levels, the awareness rates were significantly different (chi2 =14.42, P < 0.05). The total formation rate of correct behavior on schistosomiasis control was 43.16%. Between men and women groups, and among groups with different ages, the formation rates were significantly different (chi2 = 21.95, 15.00, P < 0.05 for all). Totally 94.81% of the boats discharged the excrement into water directly. CONCLUSION: The formation rate of correct behavior on schistosomiasis control of boatmen was low, thus the health promotion should be enhanced for them.
Subject(s)
Health Knowledge, Attitudes, Practice , Schistosomiasis/prevention & control , Adult , Animals , China , Data Collection , Female , Humans , Male , Occupations , Rivers , Schistosoma/isolation & purificationABSTRACT
OBJECTIVE: To construct a platform for Schistosoma japonicum infection real-time monitoring and early warning in marshlands along the Yangtze River. METHODS: The data of the status of Oncomelania hupensis snails, schistosomiasis endemic situation, marshland environment status, and other basic information were collected and analyzed comprehensively in marshlands along the Yangtze River in Jiangsu Province, and a schistosomiasis endemic situation electronic map was established. Through the GPS and 3G technology, the short messaging service (SMS) alerts were sent to the fishermen when they entered the areas of different schistosomiasis endemic levels in real-time. RESULTS: The SMS alerts reminded the fishermen to adopt the suitable interventions to reduce or avoid the schistosome infection. In addition, the data of moving track of mobile phones of fishermen, and the examination and treatment of schistosomiasis at each monitoring point were collected and analyzed comprehensively and then systematic analysis reports of schistosomiasis situation prediction, early warning, related evaluation, etc. were created in real-time. CONCLUSION: The platform for Schistosoma japonicum infection real-time monitoring and early warning in marshlands along the Yangtze River has a certain application value for schistosomiasis prevention and control work of Jiangsu Province and even whole country.
