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At least 19 recordsLinked to original sources
PubMed2026

The chemical landscape of plant surface metabolites: Acylsugars as models of ecological function and structural diversity.

Plants produce a multifunctional assortment of specialized metabolites that play important roles in defense, environmental adaptation, and ecological interactions. Among these compounds, acylsugars, nonvolatile metabolites produced primarily in glandular trichomes of Solanaceae species, have emerged as informative model systems for understanding plant surface chemistry. Differences in acyl chain length, branching pattern, saturation, and attachment position generate extensive chemical diversity that influences herbivore deterrence, pathogen resistance, and the physicochemical properties of leaf surfaces. Recent advances in analytical chemistry, particularly liquid chromatography-ion mobility-tandem mass spectrometry (LC-IM-MS/MS), have greatly improved the ability to separate structurally related acylsugar isomers and characterize metabolite complexity at high resolution. When integrated with genomics, transcriptomics, and emerging spatial metabolomics approaches, these analytical tools provide new insights into acylsugar biosynthesis, pathway regulation, evolutionary diversification, and ecological function across plant species. This review positions acylsugars, particularly those of Solanum species, as model systems for understanding how structural diversity, spatial localization, and specialized metabolism shape ecological and physiological function at plant surfaces. We examine acylsugar structural diversity, biosynthetic pathways, ecological and physiological functions, and interactions with environmental and atmospheric processes. Major challenges, including extensive isomeric complexity, incomplete pathway characterization, and difficulties linking chemical structure to biological function, are discussed alongside emerging opportunities in integrative omics, crop improvement, sustainable pest management, and environmental monitoring. Overall, acylsugars provide a powerful model for linking molecular structure, spatial localization, and ecological function, offering broader insight into how specialized metabolism shapes plant adaptation, defense, and environmental interactions.

Acylsugars↗
PubMed1994

Biosynthesis of a structurally novel lipid A in Rhizobium leguminosarum: identification and characterization of six metabolic steps leading from UDP-GlcNAc to 3-deoxy-D-manno-2-octulosonic acid2-lipid IVA.

Lipopolysaccharides (LPSs) are prominent structural components of the outer membranes of gram-negative bacteria. In Rhizobium spp. LPS functions as a determinant of the nitrogen-fixing symbiosis with legumes. LPS is anchored to the outer surface of the outer membrane by the lipid A moiety, the principal lipid component of the outer bacterial surface. Several notable structural differences exist between the lipid A of Escherichia coli and that of Rhizobium leguminosarum, suggesting that diverse biosynthetic pathways may also exist. These differences include the lack of phosphate groups and the presence of a 4'-linked GalA residue in the latter. However, we now show that UDP-GlcNAc plays a key role in the biosynthesis of lipid A in R. leguminosarum, as it does in E. coli. 32P-labeled monosaccharide and disaccharide lipid A intermediates from E. coli were isolated and tested as substrates in cell extracts of R. leguminosarum biovars phaseoli and viciae. Six enzymes that catalyze the early steps of E. coli lipid A biosynthesis were also present in extracts of R. leguminosarum. Our results show that all the enzymes of the pathway leading to the formation of the intermediate 3-deoxy-D-manno-2-octulosonic acid (Kdo2)-lipid IVA are functional in both R. leguminosarum biovars. These enzymes include (i) UDP-GlcNAc 3-O-acyltransferase; (ii) UDP-3-O-(R-3-hydroxymyristoyl)-GlcNAc deacetylase; (iii) UDP-3-O-(R-3-hydroxymyristoyl)-GlcN N-acyltransferase; (iv) disaccharide synthase; (v) 4'-kinase; and (vi) Kdo transferase. Our data suggest that the early steps in lipid A biosynthesis are conserved and that the divergence leading to rhizobial lipid A may occur at a later stage in the pathway, presumably after the attachment of the Kdo residues.

Acetates↗
PubMed2005

Organic compatible solutes of halotolerant and halophilic microorganisms.

Microorganisms that adapt to moderate and high salt environments use a variety of solutes, organic and inorganic, to counter external osmotic pressure. The organic solutes can be zwitterionic, noncharged, or anionic (along with an inorganic cation such as K(+)). The range of solutes, their diverse biosynthetic pathways, and physical properties of the solutes that effect molecular stability are reviewed.

Journal Article↗
PubMed2003

The biotin enzyme family: conserved structural motifs and domain rearrangements.

The biotin carboxylase family is comprised of a group of enzymes that utilize a covalently bound prosthetic group, biotin, as a cofactor. These enzymes, which include acetyl-CoA carboxylase, pyruvate carboxylase, propionyl-CoA carboxylase, methylcrotonyl-CoA carboxylase, geranoyl-CoA carboxylase, oxaloacetate decarboxylase, methylmalonyl-CoA decarboxylase, transcarboxylase and urea amidolyase, are found in diverse biosynthetic pathways in both pro-karyotes and eukaryotes. The reactions catalyzed by most members of this group of enzymes share two common features: (1) carboxylation of biotin, apparently via the formation of a carboxyphosphate intermediate, followed by (2) transcarboxylation of CO(2) from biotin to specific acceptor molecules to yield different products. Structural determinations by NMR and X-ray crystallography, complemented by mutagenesis studies, have identified some motifs that are structurally or catalytically important. Analysis of the amino acid sequences of a number of biotin carboxylases not only shows remarkable similarities within certain domains but also that there appears to have been domain rearrangements between groups of carboxylases. Acyl-coenzyme A derivatives, which bind either as substrates or as allosteric regulators of the biotin carboxylases, do not appear to share any of the CoA binding motifs that have been identified in other CoA-SH/acyl-CoA binding proteins. Further comparisons of biotin-dependent carboxylases with other groups of enzymes in the protein data bank reveal that this family of biotin enzymes has strong similarities in specific domains to a number of ATP-utilizing enzymes and to the lipoyl-containing enzymes. These structural homologies are so extensive as to be highly suggestive of evolutionary relationships between biotin carboxylases and these other enzymes.

Acetyl-CoA Carboxylase↗
PubMed1983

Pharmacokinetics of 14C CDP-choline.

The absorption, metabolism and excretion of cytidine diphosphate choline (CDP-choline, citicoline, Somazina) were investigated in six adult healthy subjects after a single oral dose of 300 mg of the 14C-labelled compound. The compound was well tolerated by the subjects. Absorption was virtually complete with less than 1% of the dose being found in the faeces during the 5-day collection period. Two peaks were found in the plasma radioactivity time profile: the first at 1 h, and a second larger peak at 24 h post-dose. Elimination of the ingested dose occurred via respiratory CO2 and through urinary excretion; the former predominating, and both routes exhibited biphasic patterns characterized by an early phase followed by slower decline. It is postulated that in the healthy human subject CDP-choline is metabolized in the gut wall and in the liver; the products arising from the compound's extensive hepatic metabolism being subsequently available for diverse biosynthetic pathways, tissue metabolism, and excretion.

Adult↗
PubMed2004

Expression, purification, crystallization and preliminary X-ray analysis of strictosidine glucosidase, an enzyme initiating biosynthetic pathways to a unique diversity of indole alkaloid skeletons.

Strictosidine beta-D-glucosidase, a plant enzyme initiating biosynthetic pathways to about 2000 monoterpenoid indole alkaloids with an extremely large number of various carbon skeletons, has been functionally expressed in Escherichia coli and purified to homogeneity in mg scale. Crystals suitable for X-ray analysis were found by robot-mediated screening. Using the hanging-drop technique, optimum conditions were 0.3 M ammonium sulfate, 0.1 M sodium acetate, pH 4.6 and PEG 4000 (10%) as precipitant buffer. The crystals of strictosidine glucosidase belong to the space group P42(1)2 with unit cell dimensions of a=157.63, c=103.59 A and diffract X-rays to 2.48-A resolution.

Catharanthus↗
PubMed1999

Metabolic engineering of poly(3-hydroxyalkanoates): from DNA to plastic.

Poly(3-hydroxyalkanoates) (PHAs) are a class of microbially produced polyesters that have potential applications as conventional plastics, specifically thermoplastic elastomers. A wealth of biological diversity in PHA formation exists, with at least 100 different PHA constituents and at least five different dedicated PHA biosynthetic pathways. This diversity, in combination with classical microbial physiology and modern molecular biology, has now opened up this area for genetic and metabolic engineering to develop optimal PHA-producing organisms. Commercial processes for PHA production were initially developed by W. R. Grace in the 1960s and later developed by Imperial Chemical Industries, Ltd., in the United Kingdom in the 1970s and 1980s. Since the early 1990s, Metabolix Inc. and Monsanto have been the driving forces behind the commercial exploitation of PHA polymers in the United States. The gram-negative bacterium Ralstonia eutropha, formerly known as Alcaligenes eutrophus, has generally been used as the production organism of choice, and intracellular accumulation of PHA of over 90% of the cell dry weight have been reported. The advent of molecular biological techniques and a developing environmental awareness initiated a renewed scientific interest in PHAs, and the biosynthetic machinery for PHA metabolism has been studied in great detail over the last two decades. Because the structure and monomeric composition of PHAs determine the applications for each type of polymer, a variety of polymers have been synthesized by cofeeding of various substrates or by metabolic engineering of the production organism. Classical microbiology and modern molecular bacterial physiology have been brought together to decipher the intricacies of PHA metabolism both for production purposes and for the unraveling of the natural role of PHAs. This review provides an overview of the different PHA biosynthetic systems and their genetic background, followed by a detailed summation of how this natural diversity is being used to develop commercially attractive, recombinant processes for the large-scale production of PHAs.

Acetyl-CoA C-Acetyltransferase↗
PubMed2001

Biosynthetic pathway of cephabacins in Lysobacter lactamgenus: molecular and biochemical characterization of the upstream region of the gene clusters for engineering of novel antibiotics.

The cephabacins, one of the beta-lactam antibiotics, are produced by Lysobacter lactamgenus. The previous studies the cephabacin biosynthesis were limited to a gene cluster that encodes the gene products responsible for the biosynthesis of the cephem nucleus. The long-term goal of this research is to elucidate the metabolic diversity and biosynthetic pathway of cephabacins and to design and/or discover new pharmacologically active compounds by engineering the cephabacin biosynthetic pathway in L. lactamgenus. In this study, we have cloned and sequenced a 24-kb fragment of a DNA locus upstream of the previously reported but incomplete putative ORF9 of L. lactamgenus. This contains three putative ORFs (the complete ORF9, ORF10, and ORF11) transcribed in the same direction and one putative ORF (ORF12) in the opposite direction. The isolated DNA locus extends the previously cloned part of the DNA locus containing the genes responsible for biosynthesis of the cephem nucleus up to 45 kb. The 42-kb fragment of the 45-kb gene cluster is located between a potential TATA box just upstream of the ORF11 and a termination loop just downstream of the previously reported bla gene. The complete ORF9 contains three nonribosomal peptide synthetase (NRPS) modules and one polyketide synthase (PKS) module and the ORF11 contains one NRPS module. The complete ORF9 also contains a putative thioesterase domain at the C-terminal end. We predicted the amino acid specificity of the four NRPSs by generating specificity binding pockets and expressed one of the NRPSs to confirm the amino acid specificity. The adenylation domain of the NRPS1, which is the last module of the NRPSs, showed significant amino acid specificity for L-arginine. These findings are in perfect agreement with the composition that was expected for the structure of cephabacins which contain an acetate residue, an L-arginine, and one to three L-alanines at the C-3' position of the cephem nucleus of cephabacins. The ORF10, encoding a putative ABC transporter which might be involved in conferring resistance against cephabacins, was identified between the complete ORF9 and the ORF11. Therefore, the complete ORF9, ORF10, ORF11 reported here and the other genes previously reported constitute an operon for the biosynthesis of cephabacins in L. lactamgenus. Based on our results, the biosynthetic pathways of acetate and elongated peptide moieties and a mechanism by which cephabacins are assembled by connecting the peptide moiety synthesized by the gene products of the complete ORF9 and the ORF11 to the C-3' position of the cephem nucleus synthesized by the gene products of pcbAB, pcbC, cefE, cefF, and cefD have been elucidated.

Amino Acid Sequence↗
PubMed2026

The Evolutionary Maintenance of Amino Acid Prototrophy in Escherichia coli.

Escherichia coli is a prototroph and can synthesize all twenty proteinogenic amino acids when required to grow in minimal medium. There are approximately sixty protein-coding genes individually essential for amino acid synthesis. This is a large mutational target for the accumulation of detrimental mutations. E. coli can rewire biosynthetic pathways in response to mutational damage, but the limits of this capacity are poorly understood. Here, to address evolutionary robustness, we asked whether and how the phenotypes of irreversible mutations causing auxotrophy could be suppressed or bypassed in the absence of horizontal gene transfer (HGT). Spontaneous suppressors could be selected for only ten of fifty-nine mutants tested (detection limit ∼7 × 10-11). Mechanisms of suppression included regional amplifications, mutations increasing gene or operon expression, mutations relaxing enzyme specificity, and mutations causing biochemical pathway diversions. Overall, the data show that spontaneous suppression of auxotrophy caused by an irreversible mutation is an evolutionary survival mechanism relevant only to a minority of the genes essential for amino acid synthesis. As a consequence, the essential genetic foundations for amino acid prototrophy are expected to be degraded over time by mutations (Muller's ratchet) and metabolic rewiring alone will be insufficient to counteract this effect. This implies that maintaining phenotypes, including prototrophy in E. coli, and potentially other bacterial species, is likely to be reliant on HGT of housekeeping genes to counteract the effects of inevitable mutational inactivation. Accordingly, chromosomal HGT in bacteria may be critical for survival across diverse environmental niches.

Escherichia coli↗
PubMed2006

Cyanobacterial peptides - nature's own combinatorial biosynthesis.

Cyanobacterial secondary metabolites have attracted increasing scientific interest due to bioactivity of many compounds in various test systems. Among the known structures, oligopeptides are often found with many congeners sharing conserved substructures, while being highly variable in others. A major part of known oligopeptides are of non-ribosomal origin and can be grouped into classes with conserved structural properties. Thus, the overall structural diversity of cyanobacterial oligopeptides only seemingly suggests an equally high diversity of biosynthetic pathways and respective genes. For each class of peptides, some of which have been found in all major branches of the cyanobacterial evolutionary tree, homologous synthetases and genes can be inferred. This implies that non-ribosomal peptide synthetase genes are a very ancient part of the cyanobacterial genome and presumably have evolved by recombination and duplication events to reach the present structural diversity of cyanobacterial oligopeptides. In addition, peptide synthetases would appear to be an essential part of the cyanobacterial evolution and physiology. The present review presents an overview of the biosynthesis of cyanobacterial peptides and corresponding gene clusters, the structural diversity of structural types and structural variations within peptide classes, and implications for the evolution and plasticity of biosynthetic genes and the potential function of cyanobacterial peptides.

Cyanobacteria↗
PubMed1979

Prostaglandin synthetase inhibitors. Drugs which affect arachidonic acid metabolism.

Drugs may alter prostaglandin production by acting on the various pathways of arachidonic acid metabolism. The liberation of arachidonic acid from membrane-bound phospholipids, induced by the enzyme phospholipase A2, may be inhibited by mepacrine and the steroidal anti-inflammatory agents. The bio-transformation of the free arachidonic acid, by the enzyme cyclooxygenase, to the unstable endoperoxide intermediates is inhibited by non-steroidal anti-inflammatory agents. Thus, the generation of all the prostaglandin products is prevented. This action can explain the anti-inflammatory, analgesic, antipyretic actions as well as the ulcerogenic properties of these aspirin-like compounds. An alternative metabolic pathway of arachidonic acid, via the lipoxygenase system, can be inhibited by an acetylenic analogue and a newer compound, phenidone. The unstable endoperoxide intermediates can be transformed by blood platelets into the pro-aggregating products, thromboxanes. This pathway can be selectively inhibited by a variety of experimental compounds. Prostacyclin, a potent vasodilator and inhibitor of platelet aggregation is the major product of endoperoxide transformation in blood vessels. Its formation can be inhibited by lipid peroxides. Selective actions on one or more steps in arachidonic acid metabolism can lead to a different profile of the products subsequently generated. Such a diversion of biosynthetic pathways may be an underlying mechanism in certain pathological conditions, perhaps even in dysmenorrhea.

Animals↗
PubMed2002

Increasing antioxidant levels in tomatoes through modification of the flavonoid biosynthetic pathway.

Flavonoids are a diverse group of phenolic secondary metabolites that occur naturally in plants and therefore form an integral component of the human diet. Many of the compounds belonging to this group are potent antioxidants in vitro and epidemiological studies suggest a direct correlation between high flavonoid intake and decreased risk of cardiovascular disease, cancer and other age-related diseases. Enhancing flavonoid biosynthesis in chosen crops may provide new raw materials that have the potential to be used in foods designed for specific benefits to human health. Using genetic modification, it was possible to generate several tomato lines with significantly altered flavonoid content and to probe the role and importance of several key enzymatic steps in the tomato flavonoid biosynthetic pathway. Most notably an up to 78-fold increase in total fruit flavonols was achieved through ectopic expression of a single biosynthetic enzyme, chalcone isomerase. In addition, chalcone synthase and flavonol synthase transgenes were found to act synergistically to up-regulate flavonol biosynthesis significantly in tomato flesh tissues.

Acyl Coenzyme A↗
PubMed2003

The diverse bacterial origins of the Arabidopsis polyamine biosynthetic pathway.

We functionally identified the last remaining step in the plant polyamine biosynthetic pathway by expressing an Arabidopsis thaliana agmatine iminohydrolase cDNA in yeast. Inspection of the whole pathway suggests that the arginine decarboxylase, agmatine iminohydrolase, N-carbamoylputrescine amidohydrolase route to putrescine in plants was inherited from the cyanobacterial ancestor of the chloroplast. However, the rest of the pathway including ornithine decarboxylase and spermidine synthase was probably inherited from bacterial genes present in the original host cell, common ancestor of plants and animals, that acquired the cyanobacterial endosymbiont. An exception is S-adenosylmethionine decarboxylase, which may represent a eukaryote-specific enzyme form.

Amino Acid Sequence↗
PubMed2001

Genetic approaches to harvesting lichen products.

Lichens are symbiotic associations between fungi, green algae and/or cyanobacteria. They have a varied chemistry and produce many polyketide-derived compounds, including some, such as depsides and depsidones, that are rarely reported elsewhere. Although lichens have been appreciated in traditional medicines, their value has largely been ignored by the modern pharmaceutical industry because difficulties in establishing axenic cultures and conditions for rapid growth preclude their routine use in most conventional screening processes. Recently, molecular genetic techniques using PCR, genomic library construction and heterologous expression have provided an alternative approach to begin exploring the diversity of polyketide biosynthetic pathways in lichens. The techniques can be expanded to cover other pathway types and be integrated with conventional culture collection-based screening to provide a comprehensive search for novel chemical entities in these organisms.

Amino Acid Sequence↗
PubMed2002

The polyketide synthase gene pks4 from Gibberella fujikuroi encodes a key enzyme in the biosynthesis of the red pigment bikaverin.

The ascomycete Gibberella fujikuroi mating population C (MP-C) is well known for the production of gibberellins, but also produces many other secondary metabolites, including the red polyketide pigment bikaverin. Here, we used a differential display method to clone a polyketide synthase gene pks4 responsible for the first step of bikaverin biosynthesis. Sequence analysis indicated that pks4 encoded a 2009-amino acid polypeptide consisting of four functional domains: beta-ketoacyl synthase (KS), acyltransferase (AT), acyl carrier (ACP), and thioesterase (TE). Disruption of pks4 resulted in the loss of both pks4 transcripts and bikaverin biosynthesis in G. fujikuroi cultures. Expression of pks4 is strongly repressed by high amounts of ammonium and basic pH. Unexpectedly, pks4 was overexpressed in mutants of the regulatory gene, areA, which is responsible for the activation of nitrogen assimilation genes. Three additional polyketide synthase genes have been cloned from G. fujikuroi MP-C by heterologous hybridization. The presence of these four PKS genes demonstrates the diversity of polyketide biosynthetic pathways in this fungus.

Amino Acid Sequence↗
PubMed2002

Mechanisms of enzymatic CbondO bond cleavages in deoxyhexose biosynthesis.

In the past few years, significant progress has been made in our understanding of the biosynthesis of deoxyhexoses. Mechanistic studies have revealed how enzymes can cleave CbondO bonds of a hexose substrate to make unusual sugars. The increasing amount of knowledge about the biosynthesis of deoxysugars may allow the assembly of a repertoire of novel sugar structures through recruitment and collaborative action of genes from a variety of biosynthetic pathways to create diverse secondary metabolites in our search for novel antibiotic/antitumour agents.

Deoxy Sugars↗
PubMed1997

A study of iterative type II polyketide synthases, using bacterial genes cloned from soil DNA: a means to access and use genes from uncultured microorganisms.

To examine as randomly as possible the role of the beta-ketoacyl and acyl carrier protein (ACP) components of bacterial type II polyketide synthases (PKSs), homologs of the chain-length-factor (CLF) genes were cloned from the environmental community of microorganisms. With PCR primers derived from conserved regions of known ketosynthase (KSalpha) and ACP genes specifying the formation of 16- to 24-carbon polyketides, two CLF (KSbeta) genes were cloned from unclassified streptomycetes isolated from the soil, and two were cloned from soil DNA without the prior isolation of the parent microorganism. The sequence and deduced product of each gene were distinct from those of known KSbeta genes and, by phylogenetic analysis, belonged to antibiotic-producing PKS gene clusters. Hybrid PKS gene cassettes were constructed with each novel KSbeta gene substituted for the actI-ORF2 or tcmL KSbeta subunit genes, along with the respective actI-ORF1 or tcmK KSalpha, tcmM ACP, and tcmN cyclase genes, and were found to produce an octaketide or decaketide product characteristic of the ones known to be made by the heterologous KSalpha gene partner. Since substantially less than 1% of the microorganisms present in soil are thought to be cultivatable by standard methods, this work demonstrates a potential way to gain access to a more extensive range of microbial molecular diversity and to biosynthetic pathways whose products can be tested for biological applications.

Acyl Carrier Protein↗
PubMed1986

The general control of amino acid biosynthetic genes in the yeast Saccharomyces cerevisiae.

Enzymes in diverse amino acid biosynthetic pathways in Saccharomyces cerevisiae are subject to a general amino acid control in which starvation for any amino acid leads to increased levels of the mRNAs encoding these enzymes. The short nucleotide sequence TGACTC, found nontandemly repeated upstream from the coregulated structural genes, serves as a cis-acting site for positive regulation of transcription. Multiple trans-acting repressors and activators have been identified. Most of these factors act indirectly by regulating the level of an activator encoded by the GCN4 gene. This regulation occurs at the level of GCN4 translation and is mediated by sequences in the long 5' leader of GCN4 mRNA. The GCN4 protein is the most likely candidate for the transcriptional activator that interacts with the TGACTC sequences at the structural genes.

Amino Acids↗