Compounds of polyketide origin possess a wealth of pharmacological effects, including antibacterial, antifungal, antiparasitic, anticancer and immunosuppressive activities. Many of these compounds and their semisynthetic derivatives are used today in the clinic. Most of the gene clusters encoding commercially important drugs have also been cloned and sequenced and their biosynthetic mechanisms studied in great detail. The area of biosynthetic engineering of the enzymes involved in polyketide biosynthesis has recently advanced and been transferred into the industrial arena. In this work, we introduce a computational system to provide the user with a wealth of information that can be utilized for biosynthetic engineering of enzymes involved in post-PKS tailoring steps. Post-PKS tailoring steps are necessary to add functional groups essential for the biological activity and are therefore important in polyketide biosynthesis.
Clone Cells ; Multigene Family

Microarray technology enables us to measure the expression of tens of thousands of genes simultaneously under various experimental conditions. Clustering analysis is one of the most successful methods for analyzing microarray data using the assumption that co-expressed genes may be co-regulated. It is important to extract meaningful clusters from a long unordered list of clusters and to evaluate the functional homogeneity and heterogeneity of clusters. Many quality measures for clustering results have been suggested in different conditions. In the present study, we consider biological pathways as a collection of biological knowledge and used them as a reference for measuring the quality of clustering results and functional homogeneities. PathTalk visualizes and evaluates functional relationships between gene clusters and biological pathways.
Cluster Analysis ; Multigene Family ; Population Characteristics ; Transcutaneous Electric Nerve Stimulation

The genes that codify the subunits of the fibril-forming collagen constitute an evolutionarily related group within the collagen multigene family, Deposition of fibrillar molecules in the extrcellular matrix of several tissues influences a number of cellular activities such as adhesion, proliferation, and migration. In the developing and adult organisms, temporal and spatial expression of collasgen genes is modulated by a variety of cytokines and hormones, Likewise, transcription of collagen genes in tissue cultures can be greatly affected by the action of these substances and by chemical or viral transformation as well. Cytokine-mediated increase of collagen deposition on response to environmental stimuli is also the major histopathological feature of clinically distinct that similarly lead to overt firrotic processes. It is my heartily with to elucidate the mechanisms that regulate tissue specific expression of the human collagen genes a prerequisite for understanding the pathophysiology of diseased processes. Involving collagen metabolism, such as scleroderma.
Adult ; Collagen* ; Cytokines ; Gene Expression* ; Humans ; Metabolism ; Multigene Family ; Psoriasis

Streptomyces are major sources of bioactive natural products. Genome sequencing reveals that Streptomyces have great biosynthetic potential, with an average of 20-40 biosynthetic gene clusters each strain. However, most natural products from Streptomyces are produced in low yields under regular laboratory cultivation conditions, which hamper their further study and drug development. The production of natural products in Streptomyces is controlled by the intricate regulation mechanisms. Manipulation of the regulatory systems that govern secondary metabolite production will strongly facilitate the discovery and development of natural products of Streptomyces origin. In this review, we summarize progresses in pathway-specific regulators from Streptomyces in the last five years and highlight their role in improving the yields of corresponding natural products.
Biological Products ; Multigene Family ; Secondary Metabolism ; Streptomyces/genetics*

Over-expression of the pathway specific positive regulator gene is an effective way to activate silent gene cluster. In the curret study, the SARP family regulatory gene, vasR2, was over-expressed in strain Verrucosispora sp. NS0172 and the cryptic gene cluster responsible for the biosynthesis of pentaketide ansamycin was partially activated. Two tetraketides (1 and 2) and a triketide (3) ansamycins, together with five known compounds (4-8), were isolated and elucidated from strain NS0172OEvasR2. Their NMR data were completely assigned by analysis of their HR-ESI-MS and
Micromonosporaceae/metabolism* ; Multigene Family ; Polyketides/metabolism* ; Rifabutin/metabolism*

Streptomyces aureofaciens DM-1 is a high-yielding 6-demethylchlortetracycline producer. The genome sequencing of DM-1 reveals a linear chromosome containing 6 824 334 bps nucleotides with GC content of 72.6%. In this genome, a total of 6 431 open reading frames were predicted by using glimmer 3.02, Genemark and Z-Curve softwares. Twenty-eight secondary metabolite biosynthetic gene clusters were uncovered by using AntiSMASH gene prediction software, including the complete 6-demethylchlortetracycline biosynthetic gene cluster. A frame-shift mutation in methyltransferase coding region was detected, which may result in the demethylation of chlortetracycline. The complete genome sequence of S. aureofaciens DM-1 provides basic information for functional genomics studies and selection of high-yielding strains for 6-demethylchlortetracycline.
Base Sequence ; Chlortetracycline ; Demeclocycline ; Multigene Family/genetics* ; Streptomyces aureofaciens/genetics*

Xanthocillin is a unique natural product with an isonitrile group and shows remarkable antibacterial activity. In this study, the genome of an endophytic fungus Penicillium chrysogenum MT-40 isolated from Huperzia serrata was sequenced, and the gene clusters with the potential to synthesize xanthocillin analogues were mined by local BLAST and various bioinformatics analysis tools. As a result, a biosynthetic gene cluster (named for) responsible for the biosynthesis of xanthocillin analogues was identified by further heterologous expression of the key genes in Aspergillus oryzae NSAR1. Specifically, the ForB catalyzes the synthesis of 2-formamido-3-(4-hydroxyphenyl) acrylic acid, and the ForG catalyzes the dimerization of 2-formamido-3-(4-hydroxyphenyl) acrylic acid to produce the xanthocillin analogue N, N'-(1, 4-bis (4-hydroxyphenyl) buta-1, 3-diene-2, 3-diyl) diformamide. The results reported here provide a reference for further discovery of xanthocillin analogues from fungi.
Penicillium chrysogenum/genetics* ; Huperzia/microbiology* ; Acrylates ; Multigene Family

Lipoxygenases (linoleate: oxygen oxidoreductase, EC 1.13.11.12; LOXs) are encoded by a multi-gene family in plants. The LOXs are monomeric non-heme, non-sulfur iron dioxygenases, which catalyze the incorporation of molecular oxygen into polyunsaturated fatty acids containing a cis, cis-1,4-pentadiene moiety. The LOX isoforms are distinguished by differences in optimum pH of the reaction, pI, substrate and product specificity, spatial and temporal expression, and subcellular localization. The function of various LOXs in plants has been suggested. Some of the physiological processes in which lipoxygenases have been implicated include wounding, pathogen attack, seed germination, fruit ripening, plant senescence, and synthesis of Abscisic acid (ABA) and Jasmonic acid (JA). During normal vegetative and reproductive growth, lipoxygenases have also been suggested to act as vegetative storage proteins, participate in transference of lipoid, and response to nutrient stress and source/sink relationships. Significant progress in understanding LOX families will be beneficial to the application of the LOX in crop breeding, research on new-type phytoalexin and food industry.
Gene Expression Regulation, Plant ; Lipoxygenase ; genetics ; metabolism ; Multigene Family ; Plants ; enzymology ; Protein Isoforms ; genetics ; metabolism

OBJECTIVETo review the research progress on Type IV secretion system (T4SS) in Helicobacter pylori.

DATA SOURCESThe data used in this review were identified by searching of PUBMED (1995 - 2007) online resources using the key terms 'Type IV secretion system' and 'Helicobacter pylori'.

STUDY SELECTIONMainly original articles and critical reviews written by major pioneer investigators of this field were selected.

RESULTSThe research progress on T4SS in Helicobacter pylori was summarized. The structure and function was discussed.

CONCLUSIONST4SS is not only involved in toxin secretion and injection of virulence factors into eukaryotic host target cells, but also involved in horizontal DNA transfer to other bacteria and eukaryotic cells, through DNA uptake from or release into the extracellular milieu. It provides a new insight into the pathogenicity of Helicobacter pylori and a novel target for antimicrobials development. However, many challenges remain for us in understanding the biological role of T4SS in Helicobacter pylori.

Erythromycin A is a clinically important macrolide antibiotic with broad-spectrum activity. Its biosynthesis involves the formation of the 14-membered skeleton catalyzed by polyketide synthases, and the modification steps such as hydroxylation, glycosylation and methylation. Based on the understanding of the biosynthetic mechanism, it is reliable to genetically manipulate the erythromycin A-producing strain for production improvement and structure modification. In this paper, we reviewed the progress regarding erythromycin A in high-producing strain construction and chemical structure derivation, to provide insights for further development.
Anti-Bacterial Agents ; biosynthesis ; chemistry ; Erythromycin ; biosynthesis ; chemistry ; Glycosylation ; Hydroxylation ; Methylation ; Multigene Family ; Polyketide Synthases ; metabolism