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1.
Structural Diversification of Lyngbyatoxin A by Host‐Dependent Heterologous Expression of the tleABC Biosynthetic Gene Cluster
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Lihan Zhang Shotaro Hoshino Dr. Takayoshi Awakawa Prof. Dr. Toshiyuki Wakimoto Prof. Dr. Ikuro Abe 《Chembiochem : a European journal of chemical biology》2016,17(15):1407-1411
Natural products have enormous structural diversity, yet little is known about how such diversity is achieved in nature. Here we report the structural diversification of a cyanotoxin—lyngbyatoxin A—and its biosynthetic intermediates by heterologous expression of the Streptomyces‐derived tleABC biosynthetic gene cluster in three different Streptomyces hosts: S. lividans, S. albus, and S. avermitilis. Notably, the isolated lyngbyatoxin derivatives, including four new natural products, were biosynthesized by crosstalk between the heterologous tleABC gene cluster and the endogenous host enzymes. The simple strategy described here has expanded the structural diversity of lyngbyatoxin A and its biosynthetic intermediates, and provides opportunities for investigation of the currently underestimated hidden biosynthetic crosstalk. 相似文献
2.
Diversity of Polyketide Chains Achieved by Deleting the Tailoring Genes in the Biosynthesis of Ansatrienins
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Jianxiong Wang Dr. Xiaoman Li Chunhua Lu Prof. Yuemao Shen 《Chembiochem : a European journal of chemical biology》2018,19(3):256-262
The ast gene cluster (GenBank accession numbers KF813023.1 and KP284551) was characterized to be responsible for the biosynthesis of ansatrienins in Streptomyces sp. XZQH13, which contains astC, astF1, and astF2 genes involved in the assembly of the N‐cyclohexanoyl d ‐alanyl side chain and the hydroxylation of C‐19, respectively. Further to investigating the biosynthetic mechanism of ansatrienins, herein we constructed the mutant strains XZQH13OEΔastF2 and XZQH13OEΔastCΔastF2. Three new ansatrienin analogues, namely, ansatrienols I–K ( 1 – 3 ), along with trienomycinol ( 4 ) and 3‐O‐demethyltrienomycinol ( 5 ), were isolated from the XZQH13OEΔastCΔastF2 strain, and trienomycin A ( 6 ) and trienomycin G ( 7 ) were isolated from the XZQH13OEΔastF2 strain. Their structures were determined by a combination of high‐resolution MS (ESI) and 1D and 2D NMR spectroscopy. Accordingly, a pathway for the biosynthesis of these new ansatrienins was proposed. 相似文献
3.
Dr. Thomas Tørring Dr. Stephanie R. Shames Wooyoung Cho Prof. Craig R. Roy Prof. Jason M. Crawford 《Chembiochem : a European journal of chemical biology》2017,18(7):638-646
Legionella pneumophila, the causative agent of Legionnaires' disease, is a Gram‐negative gammaproteobacterial pathogen that infects and intracellularly replicates in human macrophages and a variety of protozoa. L. pneumophila encodes an orphan biosynthetic gene cluster (BGC) that contains isocyanide‐associated biosynthetic genes and is upregulated during infection. Because isocyanide‐functionalized metabolites are known to harbor invertebrate innate immunosuppressive activities in bacterial pathogen–insect interactions, we used pathway‐targeted molecular networking and tetrazine‐based chemoseletive ligation chemistry to characterize the metabolites from the orphan pathway in L. pneumophila. We also assessed their intracellular growth contributions in an amoeba and in murine bone‐marrow‐derived macrophages. Unexpectedly, two distinct groups of aromatic amino acid‐derived metabolites were identified from the pathway, including a known tyrosine‐derived isocyanide and a family of new N‐acyl‐l ‐histidine metabolites. 相似文献
4.
Yunchang Xie Dr. Bo Wang Jing Liu Junchao Zhou Dr. Junying Ma Dr. Hongbo Huang Prof. Dr. Jianhua Ju 《Chembiochem : a European journal of chemical biology》2012,13(18):2745-2757
Griseoviridin (GV) and viridogrisein (VG, also referred to as etamycin), produced by Streptomyces griseoviridis, are two chemically unrelated compounds belonging to the streptogramin family. Both of these natural products demonstrate broad‐spectrum antibacterial activity and constitute excellent candidates for future drug development. To elucidate the biosynthetic machinery associated with production of these two unique antibiotics, the gene cluster responsible for both GV and VG production was identified within the Streptomyces griseoviridis genome and characterized, and its function in GV and VG biosynthesis was confirmed by inactivation of 30 genes and complementation experiments. This sgv gene cluster is localized to a 105 kb DNA region that consists of 36 open reading frames (ORFs), including four nonribosomal peptide synthetases (NRPSs) for VG biosynthesis and a set of hybrid polyketide synthases (PKS)‐NRPSs with a discrete acyltransferase (AT), SgvQ, to assemble the GV backbone. The enzyme encoding genes for VG versus GV biosynthesis are separated into distinct “halves” of the cluster. A series of four genes: sgvA, sgvB, sgvC, and sgvK, were found downstream of the PKS‐NRPS; these likely code for construction of a γ‐butyrolactone (GBL)‐like molecule. GBLs and the corresponding GBL receptor systems are the highest ranked regulators that are able to coordinate the two streptomyces antibiotic regulatory protein (SARP) family positive regulators SgvR2 and SgvR3; both are key biosynthetic activators. Models of GV, VG, and GBL biosynthesis were proposed by using functional gene assignments, determined on the basis of bioinformatics analysis and further supported by in vivo gene inactivation experiments. Overall, this work provides new insights into the biosyntheses of the GV and VG streptogramins that are potentially applicable to a host of combinatorial biosynthetic scenarios. 相似文献
5.
Biosynthesis of Colabomycin E,a New Manumycin‐Family Metabolite,Involves an Unusual Chain‐Length Factor
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Dr. Kateřina Petříčková Dr. Stanislav Pospíšil Dr. Marek Kuzma Dr. Tereza Tylová Dr. Michal Jágr Petr Tomek Dr. Alica Chroňáková Eva Brabcová Dr. Ladislav Anděra Dr. Václav Krištůfek Dr. Miroslav Petříček 《Chembiochem : a European journal of chemical biology》2014,15(9):1334-1345
Colabomycin E is a new member of the manumycin‐type metabolites produced by the strain Streptomyces aureus SOK1/5‐04 and identified by genetic screening from a library of streptomycete strains. The structures of colabomycin E and accompanying congeners were resolved. The entire biosynthetic gene cluster was cloned and expressed in Streptomyces lividans. Bioinformatic analysis and mutagenic studies identified components of the biosynthetic pathway that are involved in the formation of both polyketide chains. Recombinant polyketide synthases (PKSs) assembled from the components of colabomycin E and asukamycin biosynthetic routes catalyzing the biosynthesis of “lower” carbon chains were constructed and expressed in S. aureus SOK1/5‐04 ΔcolC11–14 deletion mutant. Analysis of the metabolites produced by recombinant strains provided evidence that in both biosynthetic pathways the length of the lower carbon chain is controlled by an unusual chain‐length factor supporting biosynthesis either of a triketide in asukamycin or of a tetraketide in colabomycin E. Biological activity assays indicated that colabomycin E significantly inhibited IL‐1β release from THP‐1 cells and might thus potentially act as an anti‐inflammatory agent. 相似文献
6.
Zhi Feng Dr. Yasushi Ogasawara Satoshi Nomura Prof. Dr. Tohru Dairi 《Chembiochem : a European journal of chemical biology》2018,19(19):2045-2048
MS‐271, produced by Streptomyces sp. M‐271, is a lasso peptide natural product comprising 21 amino acid residues with a d ‐tryptophan at its C terminus. Because lasso peptides are ribosomal peptides, the biosynthesis of MS‐271, especially the mechanism of d ‐Trp introduction, is of great interest. The MS‐271 biosynthetic gene cluster was identified by draft genome sequencing of the MS‐271 producer, and it was revealed that the precursor peptide contains all 21 amino acid residues including the C‐terminal tryptophan. This suggested that the d ‐Trp residue is introduced by epimerization. Genes for modification enzymes such as a macrolactam synthetase (mslC), precursor peptide recognition element (mslB1), cysteine protease (mslB2), disulfide oxidoreductases (mslE, mslF), and a protein of unknown function (mslH) were found in the flanking region of the precursor peptide gene. Although obvious epimerase genes were absent in the cluster, heterologous expression of the putative MS‐271 cluster in Streptomyces lividans showed that it contains all the necessary genes for MS‐271 production including a gene for a new peptide epimerase. Furthermore, a gene‐deletion experiment indicated that MslB1, ‐B2, ‐C and ‐H were indispensable for MS‐271 production and that some interactions of the biosynthetic enzymes were essential for the biosynthesis of MS‐271. 相似文献
7.
Ozkan Fidan Dr. Riming Yan Gabrielle Gladstone Dr. Tong Zhou Prof. Dr. Du Zhu Prof. Dr. Jixun Zhan 《Chembiochem : a European journal of chemical biology》2018,19(13):1424-1432
Sch47554 and Sch47555 are antifungal compounds from Streptomyces sp. SCC‐2136. The availability of the biosynthetic gene cluster made it possible to track genes that encode biosynthetic enzymes responsible for the structural features of these two angucyclines. Sugar moieties play important roles in the biological activities of many natural products. An investigation into glycosyltransferases (GTs) might potentially help to diversify pharmaceutically significant drugs through combinatorial biosynthesis. Sequence analysis indicates that SchS7 is a putative C‐GT, whereas SchS9 and SchS10 are proposed to be O‐GTs. In this study, the roles of these three GTs in the biosynthesis of Sch47554 and Sch47555 are characterized. Coexpression of the aglycone and sugar biosynthetic genes with schS7 in Streptomyces lividans K4 resulted in the production of C‐glycosylated rabelomycin, which revealed that SchS7 attached a d ‐amicetose moiety to the aglycone core structure at the C‐9 position. Gene inactivation studies revealed that subsequent glycosylation steps took place in a sequential manner, in which SchS9 first attached either an l ‐aculose or l ‐amicetose moiety to 4′‐OH of the C‐glycosylated aglycone, then SchS10 transferred an l ‐aculose moiety to 3‐OH of the angucycline core. 相似文献
8.
In Vitro Reconstitution of a PKS Pathway for the Biosynthesis of Galbonolides in Streptomyces sp. LZ35
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Dr. Chao Liu Dr. Jing Zhu Dr. Yaoyao Li Juanli Zhang Dr. Chunhua Lu Dr. Haoxin Wang Prof. Dr. Yuemao Shen 《Chembiochem : a European journal of chemical biology》2015,16(6):998-1007
The galbonolides are 14‐membered macrolide antibiotics with a macrocyclic backbone similar to that of erythromycins. Galbonolides exhibit broad‐spectrum antifungal activities. Retro‐biosynthetic analysis suggests that the backbone of galbonolides is assembled by a type I modular polyketide synthase (PKS). Unexpectedly, the galbonolide biosynthetic gene cluster, gbn, in Streptomyces sp. LZ35 encodes a hybrid fatty acid synthase (FAS)‐PKS pathway. In vitro reconstitution revealed the functions of GbnA (an AT‐ACP didomain protein), GbnC (a FabH‐like enzyme), and GbnB (a novel multidomain PKS module without AT and ACP domains) responsible for assembling the backbone of galbonolides, respectively. To our knowledge, this study is the first biochemical characterization of a hybrid FAS‐PKS pathway for the biosynthesis of 14‐membered macrolides. The identification of this pathway provides insights into the evolution of PKSs and could facilitate the design of modular pools for synthetic biology. 相似文献
9.
Dr. Syed Masood Husain Dr. Andreas Präg Dr. Anton Linnenbrink Prof. Dr. Andreas Bechthold Prof. Dr. Michael Müller 《Chembiochem : a European journal of chemical biology》2020,21(6):780-784
Partially reduced aromatic polyketides are bioactive secondary metabolites or intermediates in the biosynthesis of deoxygenated aromatics. For the antibiotic GTRI-02 (mensalone) in different Streptomyces spp., biosynthesis involving the reduction of a fully aromatized acetyltrihydroxynaphthalene by a naphthol reductase has been proposed and shown in vitro with a fungal enzyme. However, more recently, GTRI-02 has been identified as a product of the ActIII biosynthetic gene cluster from Streptomyces coelicolor A3(2), for which the reduction of a linear polyketide precursor by ActIII ketoreductase, prior to cyclization and aromatization, has been suggested. We have examined three different ketoreductases from bacterial producer strains of GTRI-02 for their ability to reduce mono-, bi-, and tricyclic aromatic substrates. The enzymes reduced 1- and 2-tetralone but not other aromatic substrates. This strongly suggests a reduction of a cyclized but not yet aromatic polyketide intermediate in the biosynthesis of GTRI-02. Implications of the results for the biosynthesis of other secondary polyketidic metabolites are discussed. 相似文献
10.
Identifying the Minimal Enzymes for Unusual Carbon–Sulfur Bond Formation in Thienodolin Biosynthesis
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Yaya Wang Jiali Wang Shuqi Yu Fan Wang Dr. Hongmin Ma Dr. Changwu Yue Minghao Liu Prof. Dr. Zixin Deng Prof. Dr. Ying Huang Prof. Dr. Xudong Qu 《Chembiochem : a European journal of chemical biology》2016,17(9):799-803
Thienodolin (THN) features a tricyclic indole‐S‐hetero scaffold that encompasses two unique carbon–sulfur bonds. Although its biosynthetic gene cluster has been recently identified in Streptomyces albogriseolus, the essential enzymes for the formation of C?S bonds have been relatively unexplored. Here, we isolated and characterized a new biosynthetic gene cluster from Streptomyces sp. FXJ1.172. Heterologous expression, systematic gene inactivation, and in vitro biochemical characterization enable us to determine the minimum set of genes for THN synthesis, and an aminotransferase (ThnJ) for catalyzing the downstream conversion of tryptophan chlorination. In addition, we evaluated (and mainly excluded) a previously assumed pivotal intermediate by feeding experiments. With these results, we narrowed down four enzymes (ThnC–F) that are responsible for the two unprecedented C?S bond formations. Our study provides a solid basis for further unraveling of the unique C?S mechanisms. 相似文献
11.
Biosynthetic Gene Cluster for Surugamide A Encompasses an Unrelated Decapeptide,Surugamide F
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Akihiro Ninomiya Prof. Yohei Katsuyama Prof. Takefumi Kuranaga Masayuki Miyazaki Dr. Yuichi Nogi Prof. Shigeru Okada Prof. Toshiyuki Wakimoto Prof. Yasuo Ohnishi Prof. Shigeki Matsunaga Prof. Kentaro Takada 《Chembiochem : a European journal of chemical biology》2016,17(18):1709-1712
Genome mining is a powerful method for finding novel secondary metabolites. In our study on the biosynthetic gene cluster for the cyclic octapeptides surugamides A–E (inhibitors of cathepsin B), we found a putative gene cluster consisting of four successive non‐ribosomal peptide synthetase (NRPS) genes, surA, surB, surC, and surD. Prediction of amino acid sequence based on the NRPSs and gene inactivation revealed that surugamides A–E are produced by two NRPS genes, surA and surD, which were separated by two NRPS genes, surB and surC. The latter genes are responsible for the biosynthesis of an unrelated peptide, surugamide F. The pattern of intercalation observed in the sur genes is unprecedented. The structure of surugamide F, a linear decapeptide containing one 3‐amino‐2‐methylpropionic acid (AMPA) residue, was determined by spectroscopic methods and was confirmed by solid‐phase peptide synthesis. 相似文献
12.
Dr. Takayuki Motoyama Dr. Toshihiko Nogawa Dr. Toshiaki Hayashi Dr. Hiroshi Hirota Dr. Hiroyuki Osada 《Chembiochem : a European journal of chemical biology》2019,20(5):693-700
Most fungal secondary metabolism genes are poorly expressed under laboratory conditions. Nectriapyrones are known as secondary metabolites produced mainly by symbiotic fungi, including endophytes and plant pathogens. Herein, we show the induction of nectriapyrone production in the rice blast fungus Pyricularia oryzae. The two-component signal transduction system was disturbed by disrupting OSM1 and PoYPD1, which encoded a HOG MAP kinase and a His-containing phosphotransfer (HPt) protein, respectively. This induced the production of two polyketide compounds: nectriapyrone and its hydroxylated analogue. The nectriapyrone biosynthetic gene cluster consists of a polyketide synthase gene (NEC1) and an O-methyltransferase gene (NEC2). Overexpression of the two genes induced overproduction of nectriapyrone and five nectriapyrone analogues, including a new derivative. Nectriapyrone production was not required for the infection of rice. The structure of nectriapyrone is similar to that of the germicidins produced by Streptomyces spp., and nectriapyrone inhibited the growth of Streptomyces griseus. 相似文献
13.
Dong Jin‐Yan Li Ru He Hong‐Ping Zhang Ke‐Qin 《European Journal of Lipid Science and Technology》2005,107(11):779-785
A new ( 1 ) and a known ( 2 ) sphingolipid were isolated from mycelial cultures of Paraniesslia sp. YMF1.01400. The structures of these two isolates were elucidated as (2S,2'R,3R,3'E,4E,8E)‐1‐O‐(β‐D ‐glucopyranosyl)‐3‐hydroxyl‐2‐[N‐2'‐hydroxyl‐3'‐eico‐sadecenoyl]amino‐9‐methyl‐4,8‐octadecadiene ( 1 ) and (2S,2'R,3R,3'E,4E,8E)‐1‐O‐(β‐D ‐glucopyranosyl)‐3‐hydroxyl‐2‐[N‐2'‐hydroxyl‐3'‐octadecenoyl]amino‐9‐methyl‐4,8‐octadecadiene ( 2 ) by spectroscopic and chemical methods. In in vitro tests, both compounds showed moderate nematicidal activities against Bursaphelenchus xylophilus. This is the first report of secondary metabolites in a genus Paraniesslia aquatic fungus. 相似文献
14.
Identification and Characterization of the Streptazone E Biosynthetic Gene Cluster in Streptomyces sp. MSC090213JE08
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Shoto Ohno Dr. Yohei Katsuyama Yuka Tajima Dr. Miho Izumikawa Dr. Motoki Takagi Dr. Manabu Fujie Dr. Noriyuki Satoh Dr. Kazuo Shin‐ya Dr. Yasuo Ohnishi 《Chembiochem : a European journal of chemical biology》2015,16(16):2385-2391
Streptazone derivatives isolated from Streptomyces species are piperidine alkaloids with a cyclopenta[b]pyridine scaffold. Previous studies indicated that these compounds are polyketides, but the biosynthetic enzymes responsible for their synthesis are unknown. Here, we have identified the streptazone E biosynthetic gene cluster in Streptomyces sp. MSC090213JE08, which encodes a modular type I PKS and tailoring enzymes that include an aminotransferase, three oxidoreductases, and two putative cyclases. The functions of the six tailoring enzymes were analyzed by gene disruption, and two putative biosynthetic intermediates that accumulated in particular mutants were structurally elucidated. On the basis of these results, we propose a pathway for the biosynthesis of streptazone E in which the two putative cyclases of the nuclear transport factor 2–like superfamily are responsible for C?C bond formation coupled with epoxide ring opening to give the five‐membered ring of streptazone E. 相似文献
15.
Sphinganine‐Like Biogenesis of (E)‐1‐Nitropentadec‐1‐ene in Termite Soldiers of the Genus Prorhinotermes
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Dr. Anna Jirošová Dr. Pavel Majer Andrej Jančařík Klára Dolejšová Dr. Richard Tykva Dr. Jan Šobotník Dr. Pavel Jiroš Dr. Robert Hanus 《Chembiochem : a European journal of chemical biology》2014,15(4):533-536
In 1974, (E)‐1‐nitropentadec‐1‐ene, a strong lipophilic contact poison of soldiers of the termite genus Prorhinotermes, was the first‐described insect‐produced nitro compound. However, its biosynthesis remained unknown. In the present study, we tested the hypothesis that (E)‐1‐nitropentadec‐1‐ene biosynthesis originates with condensation of amino acids with tetradecanoic acid. By using in vivo experiments with radiolabeled and deuterium‐labeled putative precursors, we show that (E)‐1‐nitropentadec‐1‐ene is synthesized by the soldiers from glycine or L ‐serine and tetradecanoic acid. We propose and discuss three possible biosynthetic pathways. 相似文献
16.
Biosynthesis of Hygrocins,Antitumor Naphthoquinone Ansamycins Produced by Streptomyces sp. LZ35
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Dr. Shanren Li Dr. Haoxin Wang Dr. Yaoyao Li Jingjing Deng Dr. Chunhua Lu Yan Shen Prof. Dr. Yuemao Shen 《Chembiochem : a European journal of chemical biology》2014,15(1):94-102
Hygrocins are naphthoquinone ansamycins with significant antitumor activities. Here, we report the identification and characterization of the hygrocin biosynthetic gene cluster (hgc) in Streptomyces sp. LZ35. A biosynthetic pathway is proposed based on bioinformatics analysis of the hgc genes and intermediates accumulated in selected gene disruption mutants. One of the steps during the biosynthesis of hygrocins is a Baeyer–Villiger oxidation between C5 and C6, catalyzed by luciferase‐like monooxygenase homologue Hgc3. Hgc3 represents the founding member of a previously uncharacterized family of enzymes acting as Baeyer–Villiger monooxygenases. 相似文献
17.
Dr. Zhongli Xu Martin Baunach Dr. Ling Ding Huiyun Peng Jakob Franke Prof. Dr. Christian Hertweck 《Chembiochem : a European journal of chemical biology》2014,15(9):1274-1279
Divergolides are structurally diverse ansamycins produced by a bacterial endophyte (Streptomyces sp.) of the mangrove tree Bruguiera gymnorrhiza. By genomic analyses a gene locus coding for the divergolide pathway was detected. The div gene cluster encodes genes for the biosynthesis of 3‐amino‐5‐hydroxybenzoate and the rare extender units ethylmalonyl‐CoA and isobutylmalonyl‐CoA, polyketide assembly by a modular type I polyketide synthase (PKS), and enzymes involved in tailoring reactions, such as a Baeyer–Villiger oxygenase. A detailed PKS domain analysis confirmed the stereochemical integrity of the divergolides and provided valuable new insights into the formation of the diverse aromatic chromophores. The bioinformatic analyses and the isolation and full structural elucidation of four new divergolide congeners led to a revised biosynthetic model that illustrates the formation of four different types of ansamycin chromophores from a single polyketide precursor. 相似文献
18.
Fumitaka Kudo Dr. Atsushi Motegi Kazutoshi Mizoue Dr. Tadashi Eguchi Prof. Dr. 《Chembiochem : a European journal of chemical biology》2010,11(11):1574-1582
FD‐891 is a 16‐membered cytotoxic antibiotic macrolide that is especially active against human leukemia such as HL‐60 and Jurkat cells. We identified the FD‐891 biosynthetic (gfs) gene cluster from the producer Streptomyces graminofaciens A‐8890 by using typical modular type I polyketide synthase (PKS) genes as probes. The gfs gene cluster contained five typical modular type I PKS genes (gfsA, B, C, D, and E), a cytochrome P450 gene (gfsF), a methyltransferase gene (gfsG), and a regulator gene (gfsR). The gene organization of PKSs agreed well with the basic polyketide skeleton of FD‐891 including the oxidation states and α‐alkyl substituent determined by the substrate specificities of the acyltransferase (AT) domains. To clarify the involvement of the gfs genes in the FD‐891 biosynthesis, the P450 gfsF gene was inactivated; this resulted in the loss of FD‐891 production. Instead, the gfsF gene‐disrupted mutant accumulated a novel FD‐891 analogue 25‐O‐methyl‐FD‐892, which lacked the epoxide and the hydroxyl group of FD‐891. Furthermore, the recombinant GfsF enzyme coexpressed with putidaredoxin and putidaredoxin reductase converted 25‐O‐methyl‐FD‐892 into FD‐891. In the course of the GfsF reaction, 10‐deoxy‐FD‐891 was isolated as an enzymatic reaction intermediate, which was also converted into FD‐891 by GfsF. Therefore, it was clearly found that the cytochrome P450 GfsF catalyzes epoxidation and hydroxylation in a stepwise manner in the FD‐891 biosynthesis. These results clearly confirmed that the identified gfs genes are responsible for the biosynthesis of FD‐891 in S. graminofaciens. 相似文献
19.
Christine Klaus Renato Murillo Hanna Zhao Stephanie Vanner Prof. Dr. David L. Zechel Prof. Dr. Andreas Bechthold 《Chembiochem : a European journal of chemical biology》2015,16(15):2244-2252
Recently we described an unusual way of activating a cryptic gene cluster when we explored the origin of the bald phenotype of Streptomyces calvus. Complementation of S. calvus with a correct copy of bldA restored sporulation and additionally promoted production of a new natural products. In this study we report on the expression of bldA in several Streptomyces strains that have been described as “poorly sporulating” strains. In seven out of 15 cases, HPLC profiling revealed the production of new compounds, and in two cases the overproduction of known compounds. Two compounds were isolated and their structures were determined. 相似文献
20.
Characterization of Heronamide Biosynthesis Reveals a Tailoring Hydroxylase and Indicates Migrated Double Bonds
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Dr. Yiguang Zhu Dr. Wenjun Zhang Yaolong Chen Dr. Chengshan Yuan Haibo Zhang Dr. Guangtao Zhang Liang Ma Dr. Qingbo Zhang Dr. Xinpeng Tian Prof. Dr. Si Zhang Prof. Dr. Changsheng Zhang 《Chembiochem : a European journal of chemical biology》2015,16(14):2086-2093
Heronamides belong to a growing family of β‐amino acid polyketide macrolactams (βPMs) with an unsaturated side chain. The biosynthetic gene cluster for heronamide F was identified from the deep‐sea‐derived Streptomyces sp. SCSIO 03032. The involvement of the gene cluster in heronamide biosynthesis was confirmed by the functional characterization of the P450 enzyme HerO as an 8‐hydroxylase for tailoring heronamide biosynthesis. The presence of migrated double bonds in the conjugated diene‐containing side chain of heronamides was confirmed by feeding experiments with labeled small carboxylic acid molecules. This study is the first demonstration of migrated double bonds in βPMs with an unsaturated side chain. 相似文献