Genome mining targeting unique type II PKS and NRPS led to the identification of a novel class of glycopeptides named kitacinnamycins.
Oxidative rearrangements play key roles in introducing structural complexity and biological activities of natural products biosynthesized by type II polyketide synthases (PKSs). Chartreusin (1) is a potent antitumor polyketide that contains a unique rearranged pentacyclic aromatic bilactone aglycone derived from a type II PKS. Herein, we report an unprecedented dioxygenase, ChaP, that catalyzes the final α-pyrone ring formation in 1 biosynthesis using flavin-activated oxygen as an oxidant. The X-ray crystal structures of ChaP and two homologues, docking studies, and site-directed mutagenesis provided insights into the molecular basis of the oxidative rearrangement that involves two successive C-C bond cleavage steps followed by lactonization. ChaP is the first example of a dioxygenase that requires a flavin-activated oxygen as a substrate despite lacking flavin binding sites, and represents a new class in the vicinal oxygen chelate enzyme superfamily.
Cinnamoyl-containing natural products (CCNPs) are a small class of bacterial metabolites with notable bioactivities. The biosynthesis of cinnamoyl moiety has been proposed to be assembled by an unusual highly reducing (HR) type II polyketide synthases (PKS). However, the biosynthetic route, especially the cyclization step for the benzene ring formation, remains unclear. In this work, we successfully reconstituted the pathway of cinnamoyl moiety in kitacinnamycin biosynthesis through a step-wise approach in vitro and demonstrated that a three-protein complex, Kcn17–Kcn18–Kcn19, can catalyze 6π-electrocyclization followed by dehydrogenation to form the benzene ring. We found that the three-protein homologues were widely distributed among 207 HR type II PKS biosynthetic gene clusters including five known CCNPs. In contrast, in the biosynthesis of youssoufene, a cinnamoyl-containing polyene, we identified that the benzene ring formation was accomplished by a distinct orphan protein. Thus, our work resolved the long-standing mystery in cinnamoyl biosynthesis and revealed two distinct enzymes that can synthesize benzene rings via polyene precursors.
A conventional Nursing Information System (NIS), which supports the role of nurse in some areas, is typically deployed as an immobile system. However, the traditional information system can't response to patients' conditions in real-time, causing delays on the availability of this information. With the advances of information technology, mobile devices are increasingly being used to extend the human mind's limited capacity to recall and process large numbers of relevant variables and to support information management, general administration, and clinical practice. Unfortunately, there have been few studies about the combination of a well-designed small-screen interface with a personal digital assistant (PDA) in clinical nursing. Some researchers found that user interface design is an important factor in determining the usability and potential use of a mobile system. Therefore, this study proposed a systematic approach to the development of a mobile nursing information system (MNIS) based on Mobile Human-Computer Interaction (M-HCI) for use in clinical nursing. The system combines principles of small-screen interface design with user-specified requirements. In addition, the iconic functions were designed with metaphor concept that will help users learn the system more quickly with less working-memory. An experiment involving learnability testing, thinking aloud and a questionnaire investigation was conducted for evaluating the effect of MNIS on PDA. The results show that the proposed MNIS is good on learning and higher satisfaction on symbol investigation, terminology and system information.
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