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81.
Jeremy R. Lohman Ming Ma Marianne E. Cuff Lance Bigelow Jessica Bearden Gyorgy Babnigg Andrzej Joachimiak George N. Phillips Jr. Ben Shen 《Proteins》2014,82(7):1210-1218
Carrier proteins (CPs) play a critical role in the biosynthesis of various natural products, especially in nonribosomal peptide synthetase (NRPS) and polyketide synthase (PKS) enzymology, where the CPs are referred to as peptidyl‐carrier proteins (PCPs) or acyl‐carrier proteins (ACPs), respectively. CPs can either be a domain in large multifunctional polypeptides or standalone proteins, termed Type I and Type II, respectively. There have been many biochemical studies of the Type I PKS and NRPS CPs, and of Type II ACPs. However, recently a number of Type II PCPs have been found and biochemically characterized. In order to understand the possible interaction surfaces for combinatorial biosynthetic efforts we crystallized the first characterized and representative Type II PCP member, BlmI, from the bleomycin biosynthetic pathway from Streptomyces verticillus ATCC 15003. The structure is similar to CPs in general but most closely resembles PCPs. Comparisons with previously determined PCP structures in complex with catalytic domains reveals a common interaction surface. This surface is highly variable in charge and shape, which likely confers specificity for interactions. Previous nuclear magnetic resonance (NMR) analysis of a prototypical Type I PCP excised from the multimodular context revealed three conformational states. Comparison of the states with the structure of BlmI and other PCPs reveals that only one of the NMR states is found in other studies, suggesting the other two states may not be relevant. The state represented by the BlmI crystal structure can therefore serve as a model for both Type I and Type II PCPs. Proteins 2014; 82:1210–1218. © 2013 Wiley Periodicals, Inc. 相似文献
82.
The aim of this study was to investigate whether a moderate‐intensity static magnetic field (SMF) can enhance the killing effect of adriamycin (ADM) on K562 cells, and to explore the effects of SMF combined with ADM on K562 cells. We analyzed the metabolic activity of cells, cell cycle distribution, DNA damage, change in cell ultrastructure, and P‐glycoprotein (P‐gp) expression after K562 cells were exposed continuously to a uniform 8.8 mT SMF for 12 h, with or without ADM. Our results showed that the SMF combined with ADM (25 ng/ml) significantly inhibited the metabolic activity of K562 cells (P < 0.05), while neither ADM nor the SMF alone affected the metabolic activity of these cells. Cell ultrastructure was altered in the SMF + ADM group. For example, cell membrane was depressed, some protuberances were observable, and vacuoles in the cytoplasm became larger. Cells were arrested at the G2/M phase and DNA damage increased after cells were treated with the SMF plus ADM. ADM also induced the P‐gp expression. In contrast, in the SMF group and SMF + ADM group, the P‐gp expression was decreased compared with the ADM group. Taken together, our results showed that the 8.8 mT SMF enhanced the cytotoxity potency of ADM on K562 cells, and the decrease in P‐gp expression may be one reason underlying this effect. Bioelectromagnetics 32:191–199, 2011. © 2010 Wiley‐Liss, Inc. 相似文献
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Light stimulates the synthesis of amaranthin in Amaranthus caudatus var. viridis. Evidence suggests that this stimulation is markedly dependent on seedling age. Synthesis is controlled by both a “low-energy” red/far-red reversible phytochrome system and an HER at least partially under phytochrome control. In seedlings exposed to light, synthesis is promoted by exogenously applied DOPA and tyrosine. It is suggested that at least two light-promoted reactions occur in the biosynthetic pathway; one between tyrosine and DOPA and a second between DOPA and amaranthin. 相似文献
86.
Characterization of the tunicamycin gene cluster unveiling unique steps involved in its biosynthesis
Wenqing Chen Dongjing Qu Lipeng Zhai Meifeng Tao Yemin Wang Shuangjun Lin Neil P. J. Price Zixin Deng 《蛋白质与细胞》2010,1(12):1093
Tunicamycin, a potent reversible translocase I inhibitor, is produced by several Actinomycetes species. The tunicamycin structure is highly unusual, and contains an 11-carbon dialdose sugar and an α, β -1″,11′-glycosidic linkage. Here we report the identification of a gene cluster essential for tunicamycin biosynthesis by high-throughput heterologous expression (HHE) strategy combined with a bioassay. Introduction of the genes into heterologous non-producing Streptomyces hosts results in production of tunicamycin by these strains, demonstrating the role of the genes for the biosynthesis of tunicamycins. Gene disruption experiments coupled with bioinformatic analysis revealed that the tunicamycin gene cluster is minimally composed of 12 genes (tunA– tunL ). Amongst these is a putative radical SAM enzyme (Tun B) with a potentially unique role in biosynthetic carbon-carbon bond formation. Hence, a seven-step novel pathway is proposed for tunicamycin biosynthesis. Moreover, two gene clusters for the potential biosynthesis of tunicamycin-like antibiotics were also identified in Streptomyces clavuligerus ATCC 27064 and Actinosynnema mirums DSM 43827. These data provide clarification of the novel mechanisms for tunicamycin biosynthesis, and for the generation of new-designer tunicamycin analogs with selective/enhanced bioactivity via combinatorial biosynthesis strategies. 相似文献
87.
Franz Hadacek 《植物科学评论》2002,21(4):273-322
Referee: Dr. Peter B. Kaufman, Dept. of Biology, University of Michigan, Ann Arbor, MI 48109-1048 Traditionally, secondary metabolites in plants have been investigated by phytochemists. Originally classified as waste products, these compounds more recently have been investigated extensively by ecologists and pharmacologists, and many complex biological functions have been discovered. Secondary metabolites occur nearly in all living organisms, within bacteria as well as in mammals, and are especially prominent in those organisms lacking an immune system. Functions of plant secondary metabolites comprise attractants, such as color pigments and scents, repellents such as antifeedants against insects and mammals, or toxins that affect growth and development of animal and microbial predators. Conversely, insects can employ plant-synthesized compounds to their own advantage, such as signals for feeding and oviposition and location of prey. Microbes also use secondary metabolites as carbon sources, and bacteria utilize them for quorum-sensing, an aspect recently discovered. Despite the diversity of recognized functions, the biochemical processes underlying these interactions are few. Primarily, they relate to the ability of these small molecules to bind to receptor regions of various proteins such as keys into locks. This review attempts a summary of current knowledge of secondary plant metabolism with focus on history of discovery, development of analytical techniques, theories of origin and function, signal pathways, biosynthesis, and assessment of biological activities. Outlined is current utilization by, and future perspectives in, different disciplines, such as chemosystematics, chemical ecology, and agricultural biotechnology. Examples illustrate the strong potential of research in secondary metabolism, particularly in comparison to more established disciplines such as developmental biology and physiology. 相似文献
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Catharanthine and akuammicine, together with ajmalicine and strictosidine, were isolated from a culture strain of Catharanthus roseus suspension cells. The biosynthetic capability of the cultured cells to produce akuammicine, catharanthine and vindoline was confirmed by feeding experiments with dl-tryptophan-[3-14C] to yield the radioactive alkaloids. 相似文献
90.
《Cell》2021,184(22):5593-5607.e18