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1.
甾类化合物具有重要的生理医药作用,市场需求巨大。甾类化合物及其关键甾类药物通过微生物转化制备工艺较化学合成法具有区域立体选择性、减少合成步骤、缩短生产周期、提高收率以及生态友好等优点逐步被应用,然而甾类物质微生物分解代谢机制还有待进一步深入探索研究并确定。本文从甾类化合物结构种类与主要来源、生理功能、微生物转化与分解代谢机制的研究等方面进行了归纳,着重解析甾类化合物分解代谢过程关键酶系及其分子作用机制,为甾药化合物生产菌种改造与工程菌构建,以及微生物转化工业化生产工艺的开发提供参考。 相似文献
2.
Tracing the fate of steroids through a hypersaline microbial mat (Kiritimati,Kiribati/Central Pacific)
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Eukaryotic steranes are typically absent or occur in very low concentrations in Precambrian sedimentary rocks. However, it is as yet unclear whether this may reflect low source inputs or a preservational bias. For instance, it has been proposed that eukaryotic lipids were profoundly degraded in benthic microbial mats that were ubiquitous prior to the advent of vertical bioturbation in the Cambrian (“mat‐seal effect”). It is therefore important to test the microbial turnover and degradation of eukaryotic steroids in real‐world microbial mats. Here we assessed steroid inventories in different layers of a microbial mat from a hypersaline lake on Kiritimati (Central Pacific). Various eukaryote‐derived C27‐C30 steroids were detected in all mat layers. These compounds most likely entered the mat system as unsaturated sterols from the water column or the topmost mat, and were progressively altered during burial in the deeper, anoxic mat layers over c. 103 years. This is reflected by increasing proportions of saturated sterols and sterenes, as well as the presence of thiosteranes in certain horizons. Sterol alteration can partly be assigned to microbial transformation but is also due to chemical reactions promoted by the reducing environment in the deeper mat layers. Notably, however, compounds with a sterane skeleton were similarly abundant in all mat layers and their absolute concentrations did not show any systematic decrease. The observed decrease of steroid/hopanoid ratios with depth may thus rather indicate a progressive “dilution” by lipids derived from heterotrophic bacteria. Further, pyrolysis revealed that steroids, in contrast to hopanoids, were not sequestered into non‐extractable organic matter. This may lead to a preservational bias against steroids during later stages of burial. Taken together, steroid preservation in the microbial mat is not only controlled by heterotrophic degradation, but rather reflects a complex interplay of taphonomic processes. 相似文献
3.
Modern research has focused on the microbial transformation of a huge variety of organic compounds to obtain compounds of therapeutic and/or industrial interest. Microbial transformation is a useful tool for producing new compounds, as a consequence of the variety of reactions for natural products. This article describes the production of many important compounds by biotransformation. Emphasis is placed on reporting the metabolites that may be of special interest to the pharmaceutical and biotechnological industries, as well as the practical aspects of this work in the field of microbial transformations. 相似文献
4.
When Apiocrea chrysosperma is incubated with progesterone for 7 days in a peptone, yeast-extract medium, eight major metabolites are produced. Each compound has been purified and its structure determined by high-field 1D and 2D 1H nuclear magnetic resonance (NMR) spectroscopy. A clear synthetic pattern is recognisable. The products have been formed by multiple transformation reactions, usually double hydroxylations. Seven compounds are tertiary alcohols in which the hydroxyl group is located on the underside of the progesterone skeleton at either the axial 9 alpha- or the axial 14 alpha-site. One compound has hydroxyl groups at both these sites. Five metabolites are also secondary progesterone alcohols, the hydroxyl groups being at the 6 beta-, 15 alpha- or 15 beta-sites. Two compounds are monohydroxy metabolites; one is dehydrogenated in ring B and the other has lost the pregnane side-chain. The structures of the eight metabolites are 6 beta, 9 alpha-dihydroxyprogesterone; 6 beta, 14 alpha-dihydroxyprogesterone; 9 alpha, 14 alpha-dihydroxyprogesterone; 9 alpha, 15 beta-dihydroxyprogesterone, 14 alpha, 15 alpha-dihydroxyprogesterone; 14 alpha, 15 beta-dihydroxyprogesterone; 14 alpha-hydroxypregna-4,6-diene-3,20-dione and 15 alpha-hydroxyandrostene-3,17-dione. All compounds, except the last one, are biologically rare because they are not products of mammalian progesterone or androstenedione metabolism. They would be difficult to synthesise chemically. We believe that the compounds, 9 alpha, 15 beta-dihydroxyprogesterone; 14 alpha, 15 alpha-dihydroxyprogesterone and 14 alpha-hydroxypregn-4,6-diene-3,20-dione, have not been reported previously as microbial transformation products of progesterone. 相似文献
5.
Biotransformation of drugs by microbial cultures for predicting mammalian drug metabolism 总被引:6,自引:0,他引:6
This review discusses the microbial transformation studies of drugs, correlating them with the corresponding metabolism (biotransformation) in animal systems. Approaches are provided for development of microbial models for mammalian metabolism. Emphasis is placed on the potential of microorganisms to mimic mammalian metabolism and provide ways for structural elucidation and toxicological and pharmacological studies of metabolites. Microorganisms can provide difficult-to-synthesize drugs and assist in identifying metabolic pathways of drugs. 相似文献
6.
Allenic and cumulenic lipids 总被引:1,自引:0,他引:1
Nowadays, about 200 natural allenic metabolites, more than 2700 synthetic allenic compounds, and about 1300 cumulenic structures are known. The present review describes research on natural as well as some biological active allenic and cumulenic lipids and related compounds isolated from different sources. Intensive searches for new classes of pharmacologically potent agents produced by living organisms have resulted in the discovery of dozens of such compounds possessing high anticancer, cytotoxic, antibacterial, antiviral, and other activities. Known allenic and cumulenic compounds can be subdivided on several structural classes: fatty acids, hydrocarbons, terpenes, steroids, carotenoids, marine bromoallenes, peptides, aromatic, cumulenic, and miscellaneous compounds. This review emphasizes the role of natural and synthetic allenic and cumulenic lipids and other related compounds as an important source of leads for drug discovery. 相似文献
7.
Formation and physiological role of biosurfactants produced by hydrocarbon-utilizing microorganisms 总被引:13,自引:0,他引:13
Rolf K. Hommel 《Biodegradation》1990,1(2-3):107-119
Microbial growth on water-insoluble carbon sources such as hydrocarbons is accompanied by metabolic and structural alterations of the cell. The appearance of surface-active compounds (biosurfactants) in the culture medium or attached to the cell boundaries is often regarded as a prerequisite for initial interactions of hydrocarbons with the microbial cell. Under this point of view, biosurfactants produced by hydrocarbon-utilizing microorganisms, their structures and physico-chemical properties are reviewed. The production of such compounds is mostly connected with growth limitation in the late logarithmic and the stationary growth phase, in which specific enzymes are induced or derepressed. Addition of purified biosurfactants to microbial cultures resulted in inhibitory as well as in stimulatory effects on growth. Therefore, a more differentiated view of microbial production of surface-active compounds is proposed. Biosurfactants should not only be regarded as prerequisites of hydrocarbon uptake, but also as secondary metabolic products. 相似文献
8.
The enzyme inosine monophosphate dehydrogenase (IMPDH) is responsible for the rate-limiting step in guanine nucleotide biosynthesis. Because it is up-regulated in rapidly proliferating cells, human type II IMPDH is actively targeted for immunosuppressive, anticancer, and antiviral chemotherapy. The enzyme employs a random-in ordered-out kinetic mechanism where substrate or cofactor can bind first but product is only released after the cofactor leaves. Due to structural and kinetic differences between mammalian and microbial enzymes, most drugs that are successful in the inhibition of mammalian IMPDH are far less effective against the microbial forms of the enzyme. It is possible that with greater knowledge of the structural mechanism of the microbial enzymes, an effective and selective inhibitor of microbial IMPDH will be developed for use as a drug against multi-drug resistant bacteria and protists. The high-resolution crystal structures of four different complexes of IMPDH from the protozoan parasite Tritrichomonas foetus have been solved: with its substrate IMP, IMP and the inhibitor mycophenolic acid (MPA), the product XMP with MPA, and XMP with the cofactor NAD(+). In addition, a potassium ion has been located at the dimer interface. A structural model for the kinetic mechanism is proposed. 相似文献
9.
The accumulation and preservation of peat soils in Everglades freshwater marshes and mangrove swamps is an essential process
in the ecological functioning of these ecosystems. Human intervention and climate change have modified nutrient dynamics and
hydroperiod in the Everglades and peat loss due to such anthropogenic activities is evident. However, not much is known on
the molecular level regarding the biogeochemical characteristics, which allow peat to be preserved in the Everglades. Lipid
biomarkers trapped within or bound to humic-type structures can provide important geochemical information regarding the origin
and microbial transformation of OM in peat. Four lipid fractions obtained from a Cladium peat, namely the freely extractable fraction and those associated with humin, humic acid, and fulvic acid fractions, showed
clear differences in their molecular distribution suggesting different OM sources and structural and diagenetic states of
the source material. Both, higher plant derived and microbial lipids were found in association with these humic-type substances.
Most biomarker distributions suggest an increment in the microbial/terrestrial lipid ratio from the free to humin to humic
to fulvic fractions. Microbial reworking of lipids, and the incorporation of microbial biomarkers into the humic-type fractions
was evident, as well as the preservation of diagenetic byproducts. The lipid distribution associated with the fulvic acids
suggests a high degree of microbial reworking for this fraction. Evidence for this 3D structure was obtained through the presence
of the relatively high abundance of α,ω-dicarboxylic acids and phenolic and benzenecarboxylic compounds. The increment in
structural complexity of the phenolic and benzencarboxylic compounds in combination with the reduction in the carbon chain
length of the dicarboxylic acids from the free to fulvic fraction suggests the latter to be structurally the most stable,
compacted and diagenetically altered substrate. This analytical approach can now be applied to peat samples from other areas
within the Everglades ecosystem, affected differently by human intervention with the aim to assess changes in organic matter
preservation. 相似文献
10.
《Phytomedicine》2014,21(12):1597-1626
Biotransformation is an economically and ecologically viable technology which has been used extensively to modify the structures of many classes of biologically active products. The discovery of novel antimicrobial metabolites from biotransformation is an important alternative to overcome the increasing levels of drug resistance by plant and human pathogens. Monoterpenes, the main constituents of essential oils, are known for their antimicrobial activities. In 2004, Farooq, Atta-Ur-Rahman and Choudhary published a review on fungal transformation of monoterpenes which covers papers published up to 2002. The present review not only updates the previous one but also discusses the antimicrobial activities (antibacterial, antifungal and antiviral) of biotransformed compounds. 相似文献
11.
Volatile affairs in microbial interactions 总被引:1,自引:0,他引:1
Ruth Schmidt Viviane Cordovez Wietse de Boer Jos Raaijmakers Paolina Garbeva 《The ISME journal》2015,9(11):2329-2335
Microorganisms are important factors in shaping our environment. One key characteristic that has been neglected for a long time is the ability of microorganisms to release chemically diverse volatile compounds. At present, it is clear that the blend of volatiles released by microorganisms can be very complex and often includes many unknown compounds for which the chemical structures remain to be elucidated. The biggest challenge now is to unravel the biological and ecological functions of these microbial volatiles. There is increasing evidence that microbial volatiles can act as infochemicals in interactions among microbes and between microbes and their eukaryotic hosts. Here, we review and discuss recent advances in understanding the natural roles of volatiles in microbe–microbe interactions. Specific emphasis will be given to the antimicrobial activities of microbial volatiles and their effects on bacterial quorum sensing, motility, gene expression and antibiotic resistance. 相似文献
12.
Sarver JG Trendel JA Bearss NR Wang L Luniwal A Erhardt PW Viola RE 《Journal of biomolecular screening》2012,17(5):673-682
The rise in organisms resistant to existing drugs has added urgency to the search for new antimicrobial agents. Aspartate β-semialdehyde dehydrogenase (ASADH) catalyzes a critical step in an essential microbial pathway that is absent in mammals. Our laboratory is using fragment library screening to identify efficient and selective ASADH inhibitors. These preliminary agents are then tested to identify compounds with desired antimicrobial properties for further refinement. Toward this end, we have established a microplate-based, dual-assay approach using a single reagent to evaluate antibiotic activity and mammalian cell toxicity during early stage development. The bacterial assay uses nonpathogenic bacteria to allow efficacy testing without a dedicated microbial laboratory. Toxicity assays are performed with a panel of mammalian cells derived from representative susceptible tissues. These assays can be adapted to target other microbial systems, such as fungi and biofilms, and additional mammalian cell lines can be added as needed. Application of this screening approach to antibiotic standards demonstrates the ability of these assays to identify bacterial selectivity and potential toxicity issues. Tests with selected agents from the ASADH inhibitor fragment library show some compounds with antibiotic activity, but as expected, most of these early agents display higher than desired mammalian cell toxicity. 相似文献
13.
Chemical and microbial degradation of the nematicides-insecticides aldicarb and ethoprop has been studied extensively in both laboratory and field studies. These studies show that temperature is the most important variable affecting the degradation rate of aldicarb and its carbamate metabolites in surface soils. Temperature and organic matter appear to be the most important variables affecting degradation rates of ethoprop in soils under normal agricultural conditions, with organic matter being inversely related to degradation, presumably due to increased binding to soil particles. Soil moisture may be important under some conditions for both compounds, with degradation reduced in low-moisture soils. The rate of degradation of aldicarb residues (aldicarb + aldicarb sulfoxide + aldicarb sulfone) does not seem to be significantly affected by depth from soil surface, except that aldicarb residues degrade more slowly in acidic, coarse sand subsoils. Degradation of ethoprop also continues in subsurface soils, although field data are limited due to its lower mobility. Both compounds degrade in groundwater. Because microbial activity decreases with depth below soil surface, chemical processes are important components of the degradation of both aldicarb residues and ethoprop. For aldicarb, transformation to carbamate oxides in surface soils is primarily microbial, while degradation to noncarbamate compounds appears to be primarily the result of soil-catalyzed hydrolysis throughout the soil profile. For ethoprop, both chemical and microbial catalyzed hydrolysis are important in surface soils, with chemical hydrolysis becoming more important with increasing depth. 相似文献
14.
Soil architecture is the dominant control over microbially mediated decomposition processes in terrestrial ecosystems. Organic
matter is physically protected in soil so that large amounts of well-decomposable compounds can be found in the vicinity of
largely starving microbial populations. Among the mechanisms proposed to explain the phenomena of physical protection in soil
are adsorption of organics on inorganic clay surfaces and entrapment of materials in aggregates or in places inaccessible
to microbes. Indirect evidence for the existence of physical protection in soil is provided by the occurrence of a burst of
microbial activity and related increased decomposition rates following disruption of soil structures, either by natural processes
such as the remoistening of a dried soil or by human activities such as ploughing. In contrast, soil compaction has only little
effect on the transformation of 14C-glucose.
Another mechanism of control by soil structure and texture on decomposition in terrestrial ecosystems is through their impact
on microbial turnover processes. The microbial population is not only the main biological agent of decomposition in soil,
it is also an important, albeit small, pool through which most of the organic matter in soil passes.
Estimates on the relative importance of different mechanisms controlling decomposition in soil could be derived from results
of combined tracer and modelling studies. However, suitable methodology to quantify the relation between soil structure and
biological processes as a function of different types and conditions of soils is still lacking. 相似文献
15.
Eukaryotic organisms of the plant and animal kingdoms have developed evolutionarily conserved systems of defence against microbial pathogens. These systems depend on the specific recognition of microbial products or structures by molecules of the host innate immune system. The first mammalian molecules shown to be involved in innate immune recognition of, and defence against, microbial pathogens were the Toll-like receptors (TLRs). These proteins are predominantly but not exclusively located in the transmembrane region of host cells. Interestingly, mammalian hosts were subsequently found to also harbour cytosolic proteins with analogous structures and functions to plant defence molecules. The members of this protein family exhibit a tripartite domain structure and are characterized by a central nucleotide-binding oligomerization domain (NOD). Moreover, in common with TLRs, most NOD proteins possess a C-terminal leucine-rich repeat (LRR) domain, which is required for the sensing of microbial products and structures. Recently, the name 'nucleotide-binding domain and LRR' (NLR) was coined to describe this family of proteins. It is now clear that NLR proteins play key roles in the cytoplasmic recognition of whole bacteria or their products. Moreover, it has been demonstrated in animal studies that NLRs are important for host defence against bacterial infection. This review will particularly focus on two subfamilies of NLR proteins, the NODs and 'NALPs', which specifically recognize bacterial products, including cell wall peptidoglycan and flagellin. We will discuss the downstream signalling events and host cell responses to NLR recognition of such products, as well as the strategies that bacterial pathogens employ to trigger NLR signalling in host cells. Cytosolic recognition of microbial factors by NLR proteins appears to be one mechanism whereby the innate immune system is able to discriminate between pathogenic bacteria ('foe') and commensal ('friendly') members of the host microflora. 相似文献
16.
Propenylbenzenes are common aromatic compounds that are often used as starting compounds for the production of various flavours. Recently, microbial transformation has emerged as an important approach for producing natural flavours in high quantities. Because the biotransformation processes are environmentally friendly and the products are considered 'natural', flavour production using this method is attracting more and more attention. This paper reviews recent advances in the application of microbial metabolism to propenylbenzenes and in subsequent flavour production. Vanillin, a valuable aromatic compound, is used as a model to show recent progress in high-value natural flavour production. Future research should focus on metabolic-mechanism characterisation and on optimisation of biotransformation to improve the yields of target products for scale-up and industrial use. 相似文献
17.
Structure/function analyses of human sex hormone-binding globulin: effects of zinc on steroid-binding specificity 总被引:2,自引:0,他引:2
Hammond GL Avvakumov GV Muller YA 《The Journal of steroid biochemistry and molecular biology》2003,85(2-5):195-200
In humans, sex hormone-binding globulin (SHBG) binds and transports the biologically most important androgens and estrogens in the blood, and regulates the access of these steroids to their targets tissues. In addition to binding sex steroids, SHBG has specific binding sites for divalent cations including calcium and zinc. Zinc binding to a site at the entrance of the steroid-binding pocket in human SHBG has been shown to reduce its affinity for estrogens, while having no impact on the binding of C19 steroids. Crystallographic studies indicate that C18 and C19 steroids are bound in opposite orientations within the SHBG steroid-binding site, and we have obtained new information that supports a molecular model explaining the mechanism by which zinc alters the affinity of human SHBG for estrogens, by studying directly the estradiol-binding properties SHBG variants created by site-directed mutagenesis. In this model, the coordination of a zinc ion by the side chains of residues Asp65 and His136 eliminates a critical hydrogen bond between Asp65 and the hydroxyl at C3 of estrogens, such as estradiol and 2-methoxyestradiol, and causes disorder in a polypeptide loop segment that covers the steroid-binding site. The combination of these structural changes explains the specific decrease in the affinity of human SHBG for C18 steroids in the presence of a zinc ion. 相似文献
18.
The metabolic fate of drugs and other xenobiotics in mammalian organisms represents an area of intense contemporary interest. Traditionally, it is a difficult area of research becausethe biological systems which are used to study biotransformations are capable of yielding only minute quantities of metabolites. Recent developments in comparative biochemistry have made itpossible to link diverse metabolic systems through similarities in the pathways by which they alter foreign organic compounds. The potential thus exists for utilizing microbial metabolic systems to study and possibly predict the metabolic fate of a drug or other foreign compound in mammals. The ease with which microbial systems may be used to obtain large amounts of metabolites is an obvious Advantage. We havhe attemped to review the ways in which mammalian and microbialorganisms metabolize a variety of organic compounds. Attention has been focused on the similarities and differences in the mechanisms by which these living systems metabolize xenobiotics. Particular emphasis has been given to four types of reactions which are important in drug biotransformations: aromatic hydroxylationl; N- and O-dealkylations; and sulfur oxygenations. 相似文献
19.
Rachel Gregor Maraike Probst Stav Eyal Alexander Aksenov Goor Sasson Igal Horovitz Pieter C. Dorrestein Michael M. Meijler Itzhak Mizrahi 《The ISME journal》2022,16(5):1262
In the past decade, studies on the mammalian gut microbiome have revealed that different animal species have distinct gut microbial compositions. The functional ramifications of this variation in microbial composition remain unclear: do these taxonomic differences indicate microbial adaptations to host-specific functionality, or are these diverse microbial communities essentially functionally redundant, as has been indicated by previous metagenomics studies? Here, we examine the metabolic content of mammalian gut microbiomes as a direct window into ecosystem function, using an untargeted metabolomics platform to analyze 101 fecal samples from a range of 25 exotic mammalian species in collaboration with a zoological center. We find that mammalian metabolomes are chemically diverse and strongly linked to microbiome composition, and that metabolome composition is further correlated to the phylogeny of the mammalian host. Specific metabolites enriched in different animal species included modified and degraded host and dietary compounds such as bile acids and triterpenoids, as well as fermentation products such as lactate and short-chain fatty acids. Our results suggest that differences in microbial taxonomic composition are indeed translated to host-specific metabolism, indicating that taxonomically distant microbiomes are more functionally diverse than redundant.Subject terms: Metabolomics, Microbiome, Microbial ecology 相似文献
20.
This review summarizes the recent research development on mammalian sialidase molecular cloning. Sialic acid–containing compounds are involved in several physiological processes, and sialidases, as glycohydrolytic enzymes that remove sialic acid residues, play a pivotal role as well. Sialidases hydrolyze the nonreducing, terminal sialic acid linkage in various natural substrates, such as glycoproteins, glycolipids, gangliosides, and polysaccharides. Mammalian sialidases are present in several tissues/organs and cells with a typical subcellular distribution: they are the lysosomal, the cytosolic, and the plasma membrane–associated sialidases. Starting in 1993, 12 different mammalian sialidases have been cloned and sequenced. A comparison of their amino acid sequences revealed the presence of highly conserved regions. These conserved regions are shared with viral and microbial sialidases that have been characterized at three-dimensional structural level, allowing us to perform the molecular modeling of the mammalian proteins and suggesting a monophyletic origin of the sialidase enzymes. Overall, the availability of the cDNA species encoding mammalian sialidases is an important step leading toward a comprehensive picture of the relationships between the structure and biological function of these enzymes. 相似文献