共查询到20条相似文献,搜索用时 15 毫秒
1.
Takuya Ito Dr. Niran Roongsawang Dr. Norifumi Shirasaka Dr. Wanli Lu Patricia M. Flatt Dr. Noer Kasanah Dr. Cristobal Miranda Dr. Taifo Mahmud Prof. Dr. 《Chembiochem : a European journal of chemical biology》2009,10(13):2253-2265
Pactamycin is an aminocyclopentitol‐derived natural product that has potent antibacterial and antitumor activities. Sequence analysis of an 86 kb continuous region of the chromosome from Streptomyces pactum ATCC 27456 revealed a gene cluster involved in the biosynthesis of pactamycin. Gene inactivation of the Fe‐S radical SAM oxidoreductase (ptmC) and the glycosyltransferase (ptmJ), individually abrogated pactamycin biosynthesis; this confirmed the involvement of the ptm gene cluster in pactamycin biosynthesis. The polyketide synthase gene (ptmQ) was found to support 6‐methylsalicylic acid (6‐MSA) synthesis in a heterologous host, S. lividans T7. In vivo inactivation of ptmQ in S. pactum impaired pactamycin and pactamycate production but led to production of two new pactamycin analogues, de‐6‐MSA‐pactamycin and de‐6‐MSA‐pactamycate. The new compounds showed equivalent cytotoxic and antibacterial activities with the corresponding parent molecules and shed more light on the structure–activity relationship of pactamycin. 相似文献
2.
Prof. Dr. Fumitaka Kudo Jiahao Zhang Shusuke Sato Dr. Akane Hirayama Prof. Dr. Tadashi Eguchi 《Chembiochem : a European journal of chemical biology》2019,20(19):2458-2462
Pactamycin is an antibiotic produced by Streptomyces pactum with antitumor and antimalarial properties. Pactamycin has a unique aminocyclitol core that is decorated with 3-aminoacetophenone, 6-methylsaliciate, and an N,N-dimethylcarbamoyl group. Herein, we show that the adenylation enzyme PctU activates 3-aminobenzoic acid (3ABA) with adenosine triphosphate and ligates it to the holo form of the discrete acyl carrier protein PctK to yield 3ABA-PctK. Then, 3ABA-PctK is N-glycosylated with uridine diphosphate-N-acetyl-d -glucosamine (UDP-GlcNAc) by the glycosyltransferase PctL to yield GlcNAc-3ABA-PctK. Because 3ABA is known to be a precursor of the 3-aminoacetophenone moiety, PctU appears to be a gatekeeper that selects the appropriate 3-aminobenzoate starter unit. Overall, we propose that acyl carrier protein-bound glycosylated 3ABA derivatives are biosynthetic intermediates of pactamycin biosynthesis. 相似文献
3.
NAD+‐Dependent Dehydrogenase PctP and Pyridoxal 5′‐Phosphate Dependent Aminotransferase PctC Catalyze the First Postglycosylation Modification of the Sugar Intermediate in Pactamycin Biosynthesis 下载免费PDF全文
Dr. Akane Hirayama Jinmiao Chu Ena Goto Dr. Fumitaka Kudo Prof. Dr. Tadashi Eguchi 《Chembiochem : a European journal of chemical biology》2018,19(2):126-130
The unique five‐membered aminocyclitol core of the antitumor antibiotic pactamycin originates from d ‐glucose, so unprecedented enzymatic modifications of the sugar intermediate are involved in the biosynthesis. However, the order of the modification reactions remains elusive. Herein, we examined the timing of introduction of an amino group into certain sugar‐derived intermediates by using recombinant enzymes that were encoded in the pactamycin biosynthesis gene cluster. We found that the NAD+‐dependent alcohol dehydrogenase PctP and pyridoxal 5′‐phosphate dependent aminotransferase PctC converted N‐acetyl‐d ‐glucosaminyl‐3‐aminoacetophonone into 3′‐amino‐3′‐deoxy‐N‐acetyl‐d ‐glucosaminyl‐3‐aminoacetophenone. Further, N‐acetyl‐d ‐glucosaminyl‐3‐aminophenyl‐β‐oxopropanoic acid ethyl ester was converted into the corresponding 3′‐amino derivative. However, PctP did not oxidize most of the tested d ‐glucose derivatives, including UDP‐GlcNAc. Thus, modification of the GlcNAc moiety in pactamycin biosynthesis appears to occur after the glycosylation of aniline derivatives. 相似文献
4.
Harnessing the Synthetic Capabilities of Glycopeptide Antibiotic Tailoring Enzymes: Characterization of the UK‐68,597 Biosynthetic Cluster 下载免费PDF全文
Grace Yim Lindsay Kalan Kalinka Koteva Maulik N. Thaker Nicholas Waglechner Irene Tang Dr. Gerard D. Wright 《Chembiochem : a European journal of chemical biology》2014,15(17):2613-2623
In this study, a draft genome sequence of Actinoplanes sp. ATCC 53533 was assembled, and an 81‐kb biosynthetic cluster for the unusual sulfated glycopeptide UK‐68,597 was identified. Glycopeptide antibiotics are important in the treatment of infections caused by Gram‐positive bacteria. Glycopeptides contain heptapeptide backbones that are modified by many tailoring enzymes, including glycosyltransferases, sulfotransferases, methyltransferases, and halogenases, generating extensive chemical and functional diversity. Several tailoring enzymes in the cluster were examined in vitro for their ability to modify glycopeptides, resulting in the synthesis of novel molecules. Tailoring enzymes were also expressed in the producer of the glycopeptide aglycone A47934, generating additional chemical diversity. This work characterizes the biosynthetic program of UK‐68,597 and demonstrates the capacity to expand glycopeptide chemical diversity by harnessing the unique chemistry of tailoring enzymes. 相似文献
5.
Jacob C. Carlson J. L. Fortman Dr. Yojiro Anzai Dr. Shengying Li Douglas A. Burr Dr. David H. Sherman Prof. 《Chembiochem : a European journal of chemical biology》2010,11(4):564-572
The structurally intriguing bicyclic ketal moiety of tirandamycin is common to several acyl‐tetramic acid antibiotics, and is a key determinant of biological activity. We have identified the tirandamycin biosynthetic gene cluster from the environmental marine isolate Streptomyces sp. 307–9, thus providing the first genetic insight into the biosynthesis of this natural product scaffold. Sequence analysis revealed a hybrid polyketide synthase–nonribosomal peptide synthetase gene cluster with a colinear domain organization, which is entirely consistent with the core structure of the tirandamycins. We also identified genes within the cluster that encode candidate tailoring enzymes for elaboration and modification of the bicyclic ketal system. Disruption of tamI, which encodes a presumed cytochrome P450, led to a mutant strain deficient in production of late stage tirandamycins that instead accumulated tirandamycin C, an intermediate devoid of any post assembly‐line oxidative modifications. 相似文献
6.
Single‐Turnover Kinetics Reveal a Distinct Mode of Thiamine Diphosphate‐Dependent Catalysis in Vitamin K Biosynthesis 下载免费PDF全文
Mingming Qin Dr. Haigang Song Xin Dai Chi‐Kong Chan Prof. Wan Chan Prof. Dr. Zhihong Guo 《Chembiochem : a European journal of chemical biology》2018,19(14):1514-1522
MenD, or (1R,2S,5S,6S)‐2‐succinyl‐5‐enolpyruvyl‐6‐hydroxycyclohex‐3‐ene‐1‐carboxylate (SEPHCHC) synthase, uses a thiamine diphosphate (ThDP)‐dependent tetrahedral Breslow intermediate rather than a canonical enamine for catalysis in the biosynthesis of vitamin K. By real‐time monitoring of the cofactor chemical state with circular dichroism spectroscopy, we found that a new post‐decarboxylation intermediate was formed from a multistep process that was rate limited by binding of the α‐ketoglutarate substrate before it quickly relaxed to the characterized tetrahedral Breslow intermediate. In addition, the chemical steps leading to the reactive post‐decarboxylation intermediates were not affected by the electrophilic substrate, isochorismate, whereas release of the product was found to limit the whole catalytic process. Moreover, these intermediates are likely kinetically stabilized owing to the low biological availability of isochorismate under physiological conditions, in contrast to the tight coupling of enamine formation with binding of the electrophilic acceptor in some other ThDP‐dependent enzymes. Together with the unusual tetrahedral structure of the intermediates, these findings strongly support a new ThDP‐dependent catalytic mode distinct from canonical enamine chemistry. 相似文献
7.
Kandy Napan Dr. Shuwei Zhang Whitney Morgan Thomas Anderson Prof. Dr. Jon Y. Takemoto Prof. Dr. Jixun Zhan 《Chembiochem : a European journal of chemical biology》2014,15(15):2289-2296
Three key tailoring enzymes in pradimicin biosynthesis: PdmJ, PdmW, and PdmN, were investigated. PdmW was characterized as the C‐6 hydroxylase by structural characterization of the corresponding product, 6‐hydroxy‐G‐2A. The efficiencies of the C‐5 and C‐6 hydroxylations, catalyzed respectively by PdmJ and PdmW, were low when they were expressed individually with the early biosynthetic enzymes that form G‐2A. When these two cytochrome P450 enzymes were co‐expressed, a dihydroxylated product, 5,6‐dihydroxy‐G‐2A, was efficiently produced, indicating that these two enzymes work synergistically in pradimicin biosynthesis. Heterologously expressed PdmN in Streptomyces coelicolor CH999 converted G‐2A to JX137a by ligating a unit of D ‐alanine to the carboxyl group. PdmN has relaxed substrate specificity toward both amino acid donors and acceptors. Through combinatorial biosynthesis, a series of new pradimicin analogues were produced. 相似文献
8.
Dr. Angela H. Soeriyadi Dr. Rabia Mazmouz Dr. Russell Pickford Dr. Bakir Al-Sinawi Dr. Ralf Kellmann Dr. Leanne A. Pearson Prof. Brett A. Neilan 《Chembiochem : a European journal of chemical biology》2021,22(5):845-849
Paralytic shellfish toxins (PSTs) are neurotoxic alkaloids produced by freshwater cyanobacteria and marine dinoflagellates. Due to their antagonism of voltage-gated sodium channels in excitable cells, certain analogues are of significant pharmacological interest. The biosynthesis of the parent compound, saxitoxin, is initiated with the formation of 4-amino-3-oxo-guanidinoheptane (ethyl ketone) by an unusual polyketide synthase-like enzyme, SxtA. We have heterologously expressed SxtA from Raphidiopsis raciborskii T3 in Escherichia coli and analysed its activity in vivo. Ethyl ketone and a truncated analogue, methyl ketone, were detected by HPLC-ESI-HRMS analysis, thus suggesting that SxtA has relaxed substrate specificity in vivo. The chemical structures of these products were further verified by tandem mass spectrometry and labelled-precursor feeding with [guanidino-15N2] arginine and [1,2-13C2] acetate. These results indicate that the reactions catalysed by SxtA could give rise to multiple PST variants, including analogues of ecological and pharmacological significance. 相似文献
9.
Jürgen Rohr Prof. Dr. 《Chembiochem : a European journal of chemical biology》2010,11(4):523-532
The gene clusters responsible for the biosynthesis of two antitumor antibiotics, ravidomycin and chrysomycin, have been cloned from Streptomyces ravidus and Streptomyces albaduncus, respectively. Sequencing of the 33.28 kb DNA region of the cosmid cosRav32 and the 34.65 kb DNA region of cosChry1‐1 and cosChryF2 revealed 36 and 35 open reading frames (ORFs), respectively, harboring tandem sets of type II polyketide synthase (PKS) genes, D ‐ravidosamine and D ‐virenose biosynthetic genes, post‐PKS tailoring genes, regulatory genes, and genes of unknown function. The isolated ravidomycin gene cluster was confirmed to be involved in ravidomycin biosynthesis through the production of a new analogue of ravidomycin along with anticipated pathway intermediates and biosynthetic shunt products upon heterologous expression of the cosmid, cosRav32, in Streptomyces lividans TK24. The identity of the cluster was further verified through cross complementation of gilvocarcin V (GV) mutants. Similarly, the chrysomycin gene cluster was demonstrated to be indirectly involved in chrysomycin biosynthesis through cross‐complementation of gilvocarcin mutants deficient in the oxygenases GilOII, GilOIII, and GilOIV with the respective chrysomycin monooxygenase homologues. The ravidomycin glycosyltransferase (RavGT) appears to be able to transfer both amino‐ and neutral sugars, exemplified through the structurally distinct 6‐membered D ‐ravidosamine and 5‐membered D ‐fucofuranose, to the coumarin‐based polyketide derived backbone. These results expand the library of biosynthetic genes involved in the biosyntheses of gilvocarcin class compounds that can be used to generate novel analogues through combinatorial biosynthesis. 相似文献
10.
Sebastian W. Fuchs Florian Grundmann Dr. Michael Kurz Marcel Kaiser Prof. Dr. Helge B. Bode 《Chembiochem : a European journal of chemical biology》2014,15(4):512-516
The structure of the fabclavines—unique mixtures of nonribosomally derived peptide–polyketide hybrids connected to an unusual polyamino moiety—has been solved by detailed NMR and MS methods. These compounds have been identified in two different entomopathogenic Xenorhabdus strains, thereby leading also to the identification of the fabclavine biosynthesis gene cluster. Detailed analysis of these clusters and initial mutagenesis experiments allowed the prediction of a biosynthesis pathway in which the polyamino moiety is derived from an unusual type of fatty acid synthase that is normally involved in formation of polyunsaturated fatty acids. As fabclavines show broad‐spectrum activity against bacteria, fungi, and other eukaryotic cells, they might act as “protection factors” against all kinds of food competitors during the complex life cycle of Xenorhabdus, its nematode host, and their insect prey. 相似文献
11.
Design of S‐Allylcysteine in Situ Production and Incorporation Based on a Novel Pyrrolysyl‐tRNA Synthetase Variant 下载免费PDF全文
Dr. Matthias P. Exner Tilmann Kuenzl Tuyet Mai T. To Zhaofei Ouyang Sergej Schwagerus Michael G. Hoesl Prof. Dr. Christian P. R. Hackenberger Prof. Dr. Marga C. Lensen Prof. Dr. Sven Panke Prof. Dr. Nediljko Budisa 《Chembiochem : a European journal of chemical biology》2017,18(1):85-90
The noncanonical amino acid S‐allyl cysteine (Sac) is one of the major compounds of garlic extract and exhibits a range of biological activities. It is also a small bioorthogonal alkene tag capable of undergoing controlled chemical modifications, such as photoinduced thiol‐ene coupling or Pd‐mediated deprotection. Its small size guarantees minimal interference with protein structure and function. Here, we report a simple protocol efficiently to couple in‐situ semisynthetic biosynthesis of Sac and its incorporation into proteins in response to amber (UAG) stop codons. We exploited the exceptional malleability of pyrrolysyl‐tRNA synthetase (PylRS) and evolved an S‐allylcysteinyl‐tRNA synthetase (SacRS) capable of specifically accepting the small, polar amino acid instead of its long and bulky aliphatic natural substrate. We succeeded in generating a novel and inexpensive strategy for the incorporation of a functionally versatile amino acid. This will help in the conversion of orthogonal translation from a standard technique in academic research to industrial biotechnology. 相似文献
12.
Synthesis of C‐Glucosylated Octaketide Anthraquinones in Nicotiana benthamiana by Using a Multispecies‐Based Biosynthetic Pathway 下载免费PDF全文
Dr. Johan Andersen‐Ranberg Dr. Kenneth Thermann Kongstad Dr. Majse Nafisi Prof. Dan Staerk Finn Thyge Okkels Prof. Uffe Hasbro Mortensen Prof. Birger Lindberg Møller Dr. Rasmus John Normand Frandsen Dr. Rubini Kannangara 《Chembiochem : a European journal of chemical biology》2017,18(19):1893-1897
Carminic acid is a C‐glucosylated octaketide anthraquinone and the main constituent of the natural dye carmine (E120), possessing unique coloring, stability, and solubility properties. Despite being used since ancient times, longstanding efforts to elucidate its route of biosynthesis have been unsuccessful. Herein, a novel combination of enzymes derived from a plant (Aloe arborescens, Aa), a bacterium (Streptomyces sp. R1128, St), and an insect (Dactylopius coccus, Dc) that allows for the biosynthesis of the C‐glucosylated anthraquinone, dcII, a precursor for carminic acid, is reported. The pathway, which consists of AaOKS, StZhuI, StZhuJ, and DcUGT2, presents an alternative biosynthetic approach for the production of polyketides by using a type III polyketide synthase (PKS) and tailoring enzymes originating from a type II PKS system. The current study showcases the power of using transient expression in Nicotiana benthamiana for efficient and rapid identification of functional biosynthetic pathways, including both soluble and membrane‐bound enzymes. 相似文献
13.
Repurposing the Chemical Scaffold of the Anti‐Arthritic Drug Lobenzarit to Target Tryptophan Biosynthesis in Mycobacterium tuberculosis 下载免费PDF全文
Dr. Genevieve L. Evans Dr. Swarna A. Gamage Dr. Esther M. M. Bulloch Prof. Edward N. Baker Prof. William A. Denny Assoc. Prof. J. Shaun Lott 《Chembiochem : a European journal of chemical biology》2014,15(6):852-864
The emergence of extensively drug‐resistant strains of Mycobacterium tuberculosis (Mtb) highlights the need for new therapeutics to treat tuberculosis. We are attempting to fast‐track a targeted approach to drug design by generating analogues of a validated hit from molecular library screening that shares its chemical scaffold with a current therapeutic, the anti‐arthritic drug Lobenzarit (LBZ). Our target, anthranilate phosphoribosyltransferase (AnPRT), is an enzyme from the tryptophan biosynthetic pathway in Mtb. A bifurcated hydrogen bond was found to be a key feature of the LBZ‐like chemical scaffold and critical for enzyme inhibition. We have determined crystal structures of compounds in complex with the enzyme that indicate that the bifurcated hydrogen bond assists in orientating compounds in the correct conformation to interact with key residues in the substrate‐binding tunnel of Mtb‐AnPRT. Characterising the inhibitory potency of the hit and its analogues in different ways proved useful, due to the multiple substrates and substrate binding sites of this enzyme. Binding in a site other than the catalytic site was found to be associated with partial inhibition. An analogue, 2‐(2‐5‐methylcarboxyphenylamino)‐3‐methylbenzoic acid, that bound at the catalytic site and caused complete, rather than partial, inhibition of enzyme activity was found. Therefore, we designed and synthesised an extended version of the scaffold on the basis of this observation. The resultant compound, 2,6‐bis‐(2‐carboxyphenylamino)benzoate, is a 40‐fold more potent inhibitor of the enzyme than the original hit and provides direction for further structure‐based drug design. 相似文献
14.
Catalytic performance of methacrylate‐based poly‐4‐(dialkylamino)‐pyridines: activity prediction via NMR shifts 下载免费PDF全文
The synthesis of the 4‐(dialkylamino)pyridine derivative 3‐(4‐(pyridin‐4‐yl)piperazin‐1‐yl)propyl methacrylate and its copolymerization with n‐butyl methacrylate are presented. The catalytic activity was evaluated in the acylation of tert‐butanol with acetic anhydride yielding tert‐butyl acetate. It is observed that the activity of polymer‐attached 4‐(dimethylamino)pyridine analogues correlates remarkably well with the chemical shift of the β‐pyridyl protons. Differences in catalytic efficiency result from distinct electronic densities of the pyridine ring, while embedding the catalytically active moiety into a polymeric structure has nearly no deleterious effect on the performance. © 2015 Society of Chemical Industry 相似文献
15.
Structure,Function, and Inhibition of Staphylococcus aureus Heptaprenyl Diphosphate Synthase 下载免费PDF全文
Janish Desai Dr. Yi‐Liang Liu Hongli Wei Dr. Weidong Liu Dr. Tzu‐Ping Ko Prof. Rey‐Ting Guo Prof. Eric Oldfield 《ChemMedChem》2016,11(17):1915-1923
We report the first structure of heptaprenyl diphosphate synthase from Staphylococcus aureus (SaHepPPS), together with an investigation of its mechanism of action and inhibition. The protein is involved in the formation of menaquinone, a key electron transporter in many bacteria, including pathogens. SaHepPPS consists of a “catalytic ” subunit (SaHepPPS‐2) having two “DDXXD” motifs and a “regulatory” subunit (SaHepPPS‐1) that lacks these motifs. High concentrations of the substrates, isopentenyl diphosphate and farnesyl diphosphate, inhibit the enzyme, which is also potently inhibited by bisphosphonates. The most active inhibitors (Ki~200 nm ) were N‐alkyl analogues of zoledronate containing ~C6 alkyl side chains. They were modestly active against S. aureus cell growth, and growth inhibition was partially “rescued” by the addition of menaquinone‐7. Because SaHepPPS is essential for S. aureus cell growth, its structure is of interest in the context of the development of menaquinone biosynthesis inhibitors as potential antibiotic leads. 相似文献
16.
Polytheonamide B, isolated from the Japanese marine sponge Theonella swinhoei, is by far the largest non-ribosomal peptide known to date, and displays potent cytotoxicity. Its 48 amino acid residues include a variety of non-proteinogenic D - and L -amino acids, and the chiralities of these amino acids alternate in sequence. These structural features induce the formation of a stable β6.3-helical structure in the hydrophobic environment, giving rise to an overall tubular structure of 45 Å in length. In a biological setting, this fold is believed to transport cations across the lipid bilayer through a pore with an inner diameter of 4 Å, thereby acting as an ion channel. In this account, we describe in detail our total synthetic route to polytheonamide B. The total synthesis relies on a combination of four key stages: synthesis of eight non-proteinogenic amino acids and an N-terminus moiety, a solid phase assembly of four fragments of polytheonamide B, three Ag+-mediated couplings of the fragments, and finally, acid-promoted global deprotection. The generality and modularity of the developed strategy will enable future studies of the chemical and biological properties of this unusual ion-channel-forming peptide and its synthetic analogues. 相似文献
17.
《Chembiochem : a European journal of chemical biology》2003,4(5):357-357
The cover picture shows how a combination of recombinant synthesis and chemical synthesis has been used to obtain chemically modified proteins. N‐terminal protein segments of pro‐neuropeptide Y (proNPY) were produced as intein‐fusion proteins in Escherischia coli in order to obtain thioesters. C‐terminal segments were synthesized by parallel automated peptide synthesis and derivatized to obtain carboxyfluorescein‐ (CF) and biotin‐labeled peptides. Native chemical ligation yielded chemically modified full‐length analogues of proNPY that can be used to monitor the biosynthesis of neuropeptide Y. Futher information can be found in the article by Beck‐Sickinger and co‐workers on p. 425 ff. 相似文献
18.
A Mutasynthesis Approach with a Penicillium chrysogenum ΔroqA Strain Yields New Roquefortine D Analogues 下载免费PDF全文
Dr. Kahina Ouchaou Dr. Florian Maire Oleksandr Salo Dr. Hazrat Ali Prof. Dr. Thomas Hankemeier Prof. Dr. Gijsbert A. van der Marel Dr. Dmitri V. Filippov Prof. Dr. Roel A. L. Bovenberg Dr. Rob J. Vreeken Prof. Dr. Arnold J. M. Driessen Prof. Dr. Herman S. Overkleeft 《Chembiochem : a European journal of chemical biology》2015,16(6):915-923
Penicillium chrysogenum, which lacks the roqA gene, processes synthetic, exogenously added histidyltryptophanyldiketopiperazine (HTD) to yield a set of roquefortine‐based secondary metabolites also produced by the wild‐type strain. Feeding a number of synthetic HTD analogues to the ΔroqA strain gives rise to the biosynthesis of a number of new roquefortine D derivatives, depending on the nature of the synthetic HTD added. Besides delivering semisynthetic roquefortine analogues, the mutasynthesis studies presented here also shed light on the substrate preferences and molecular mechanisms employed by the roquefortine C/D biosynthesis gene cluster, knowledge that may be tapped for the future development of more complex semisynthetic roquefortine‐based secondary metabolites. 相似文献
19.
Christopher J. Schwalen Dr. Xinxin Feng Dr. Weidong Liu Bing O‐Dowd Dr. Tzu‐Ping Ko Christopher J. Shin Prof. Dr. Rey‐Ting Guo Prof. Dr. Douglas A. Mitchell Prof. Dr. Dr. Eric Oldfield 《Chembiochem : a European journal of chemical biology》2017,18(11):985-991
Many organisms contain head‐to‐head isoprenoid synthases; we investigated three such types of enzymes from the pathogens Neisseria meningitidis, Neisseria gonorrhoeae, and Enterococcus hirae. The E. hirae enzyme was found to produce dehydrosqualene, and we solved an inhibitor‐bound structure that revealed a fold similar to that of CrtM from Staphylococcus aureus. In contrast, the homologous proteins from Neisseria spp. carried out only the first half of the reaction, yielding presqualene diphosphate (PSPP). Based on product analyses, bioinformatics, and mutagenesis, we concluded that the Neisseria proteins were HpnDs (PSPP synthases). The differences in chemical reactivity to CrtM were due, at least in part, to the presence of a PSPP‐stabilizing arginine in the HpnDs, decreasing the rate of dehydrosqualene biosynthesis. These results show that not only S. aureus but also other bacterial pathogens contain head‐to‐head prenyl synthases, although their biological functions remain to be elucidated. 相似文献
20.
Uncovering a Glycosyltransferase Provides Insights into the Glycosylation Step during Macrolactin and Bacillaene Biosynthesis 下载免费PDF全文
Wen Qin Yang Liu Pengfei Ren Jun Zhang Dr. Huayue Li Prof. Dr. Li Tian Prof. Dr. Wenli Li 《Chembiochem : a European journal of chemical biology》2014,15(18):2747-2753
Macrolactins (MLNs) have unique structural patterns containing a 24‐membered ring lactone and diverse bioactivities. The MLN skeleton is biosynthesized via a trans‐acyl transferase (AT) type I polyketide synthase (PKS) pathway, but the tailoring steps are still unknown. Herein, we report the identification of a glycosyltransferase (GT) gene bmmGT1, which is located at different locus from the MLN gene cluster in the genome of marine‐derived Bacillus marinus B‐9987, and its functional characterization as an MLN GT, thus affording five novel MLNs analogues. Surprisingly, this GT is also capable of catalyzing the glycosylation of bacillaenes (BAEs), which are the prototypes of trans‐AT polyketides, thus suggesting broad substrate flexibility. These results provide the first significant insights into the glycosylation step in MLN and BAE biosynthetic pathways. 相似文献