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41.
Inside Cover: Biosynthetic Gene Cluster for Surugamide A Encompasses an Unrelated Decapeptide,Surugamide F (ChemBioChem 18/2016) 下载免费PDF全文
42.
Functional Characterization of PyrG,an Unusual Nonribosomal Peptide Synthetase Module from the Pyridomycin Biosynthetic Pathway 下载免费PDF全文
Dr. Tingting Huang Lili Li Dr. Nelson L. Brock Prof. Dr. Zixin Deng Prof. Dr. Shuangjun Lin 《Chembiochem : a European journal of chemical biology》2016,17(15):1421-1425
Pyridomycin is an antimycobacterial cyclodepsipeptide assembled by a nonribosomal peptide synthetase/polyketide synthase hybrid system. Analysis of its cluster revealed a nonribosomal peptide synthetase (NRPS) module, PyrG, that contains two tandem adenylation domains and a PKS‐type ketoreductase domain. In this study, we biochemically validated that the second A domain recognizes and activates α‐keto‐β‐methylvaleric acid (2‐KVC) as the native substrate; the first A domain was not functional but might play a structural role. The KR domain catalyzed the reduction of the 2‐KVC tethered to the peptidyl carrier protein of PyrG in the presence of the MbtH family protein, PyrH. PyrG was demonstrated to recognize many amino acids. This substrate promiscuity provides the potential to generate pyridomycin analogues with various enolic acids moiety; this is important for binding InhA, a critical enzyme for cell‐wall biosynthesis in Mycobacterium tuberculosis. 相似文献
43.
Biosynthesis of Trehangelin in Polymorphospora rubra K07–0510: Identification of Metabolic Pathway to Angelyl‐CoA 下载免费PDF全文
Dr. Yuki Inahashi Taro Shiraishi Dr. Kaia Palm Prof. Dr. Yoko Takahashi Prof. Dr. Satoshi Ōmura Prof. Dr. Tomohisa Kuzuyama Dr. Takuji Nakashima 《Chembiochem : a European journal of chemical biology》2016,17(15):1442-1447
Trehangelins are trehalose angelates discovered from endophytic actinomycete Polymorphospora rubra K07‐0510. We identified the trehangelin biosynthetic gene cluster, including genes that encode a glycoside hydrolase‐like protein (thgC), α‐amylase (thgD), 3‐ketoacyl‐ACP synthase III (thgI), 3‐ketoacyl‐ACP reductase (thgK), enoyl‐CoA hydratase (thgH) and acyl transferase (thgJ). Heterologous expression of thgH, thgI, thgJ and thgK confirmed the importance of these genes in the biosynthesis of trehangelin A. Enzymatic activity studies showed that ThgI catalyses the condensation of acetyl‐CoA and methylmalonyl‐CoA to 2‐methylacetoacetyl‐CoA (MAA‐CoA), ThgK catalyses NADPH‐dependent reduction of MAA‐CoA to 3‐hydroxy‐2‐methylbutyryl‐CoA (HMB‐CoA) and ThgH catalyses the dehydration of HMB‐CoA to angelyl‐CoA (AN‐CoA). This is the first report on the elucidation of the enzymatic formation of AN‐CoA. 相似文献
44.
45.
Initial Molecular Recognition Steps of McjA Precursor during Microcin J25 Lasso Peptide Maturation 下载免费PDF全文
Dr. Nadine Assrir Dr. Anna Pavelkova Régine Dazzoni Dr. Rémi Ducasse Dr. Nelly Morellet Dr. Eric Guittet Prof. Sylvie Rebuffat Dr. Séverine Zirah Dr. Yanyan Li Dr. Ewen Lescop 《Chembiochem : a European journal of chemical biology》2016,17(19):1851-1858
Microcin J25 (MccJ25) has emerged as an excellent model to understand the maturation of ribosomal precursor peptides into the entangled lasso fold. MccJ25 biosynthesis relies on the post‐translational modification of the precursor McjA by the ATP‐dependent protease McjB and the lactam synthetase McjC. Here, using NMR spectroscopy, we showed that McjA is an intrinsically disordered protein without detectable conformational preference, which emphasizes the active role of the maturation machinery on the three‐dimensional folding of MccJ25. We further showed that the N‐terminal region of the leader peptide is involved in interaction with both maturation enzymes and identified a predominant interaction of V43–S55 in the core McjA sequence with McjC. Moreover, we demonstrated that residues K23–Q34 in the N‐terminal McjA leader peptide tend to adopt a helical conformation in the presence of membrane mimics, implying a role in directing McjA to the membrane in the vicinity of the lasso synthetase/export machinery. These data provide valuable insights into the initial molecular recognition steps in the MccJ25 maturation process. 相似文献
46.
Greg Mann Dr. Liujie Huo Sebastian Adam Dr. Brunello Nardone Dr. Jeremie Vendome Prof. Nicholas James Westwood Prof. Rolf Müller Dr. Jesko Koehnke 《Chembiochem : a European journal of chemical biology》2016,17(23):2286-2292
The bottromycins are a family of highly modified peptide natural products, which display potent antimicrobial activity against Gram‐positive bacteria, including methicillin‐resistant Staphylococcus aureus. Bottromycins have recently been shown to be ribosomally synthesized and post‐translationally modified peptides (RiPPs). Unique amongst RiPPs, the precursor peptide BotA contains a C‐terminal “follower” sequence, rather than the canonical N‐terminal “leader” sequence. We report herein the structural and biochemical characterization of BotP, a leucyl‐aminopeptidase‐like enzyme from the bottromycin pathway. We demonstrate that BotP is responsible for the removal of the N‐terminal methionine from the precursor peptide. Determining the crystal structures of both apo BotP and BotP in complex with Mn2+ allowed us to model a BotP/substrate complex and to rationalize substrate recognition. Our data represent the first step towards targeted compound modification to unlock the full antibiotic potential of bottro‐ mycin. 相似文献
47.
Interrogating the Tailoring Steps of Pactamycin Biosynthesis and Accessing New Pactamycin Analogues 下载免费PDF全文
Dr. Mostafa E. Abugrain Dr. Wanli Lu Dr. Yuexin Li Dr. Jeffrey D. Serrill Corey J. Brumsted Andrew R. Osborn Prof. Dr. Adam Alani Prof. Dr. Jane E. Ishmael Prof. Dr. Jane X. Kelly Prof. Dr. Taifo Mahmud 《Chembiochem : a European journal of chemical biology》2016,17(17):1585-1588
Pactamycin is a bacteria‐derived aminocyclitol antibiotic with a wide‐range of biological activity. Its chemical structure and potent biological activities have made it an interesting lead compound for drug discovery and development. Despite its unusual chemical structure, many aspects of its formation in nature remain elusive. Using a combination of genetic inactivation and metabolic analysis, we investigated the tailoring processes of pactamycin biosynthesis in Streptomyces pactum. The results provide insights into the sequence of events during the tailoring steps of pactamycin biosynthesis and explain the unusual production of various pactamycin analogues by S. pactum mutants. We also identified two new pactamycin analogues that have better selectivity indexes than pactamycin against malarial parasites. 相似文献
48.
The Role of a Nonribosomal Peptide Synthetase in l‐Lysine Lactamization During Capuramycin Biosynthesis 下载免费PDF全文
Dr. Xiaodong Liu Yuanyuan Jin Zheng Cui Dr. Koichi Nonaka Satoshi Baba Dr. Masanori Funabashi Dr. Zhaoyong Yang Dr. Steven G. Van Lanen 《Chembiochem : a European journal of chemical biology》2016,17(9):804-810
Capuramycins are one of several known classes of natural products that contain an l ‐Lys‐derived l ‐α‐amino‐?‐caprolactam (l ‐ACL) unit. The α‐amino group of l ‐ACL in a capuramycin is linked to an unsaturated hexuronic acid component through an amide bond that was previously shown to originate by an ATP‐independent enzymatic route. With the aid of a combined in vivo and in vitro approach, a predicted tridomain nonribosomal peptide synthetase CapU is functionally characterized here as the ATP‐dependent amide‐bond‐forming catalyst responsible for the biosynthesis of the remaining amide bond present in l ‐ACL. The results are consistent with the adenylation domain of CapU as the essential catalytic component for l ‐Lys activation and thioesterification of the adjacent thiolation domain. However, in contrast to expectations, lactamization does not require any additional domains or proteins and is likely a nonenzymatic event. The results set the stage for examining whether a similar NRPS‐mediated mechanism is employed in the biosynthesis of other l ‐ACL‐containing natural products and, just as intriguingly, how spontaneous lactamization is avoided in the numerous NRPS‐derived peptides that contain an unmodified l ‐Lys residue. 相似文献
49.
Cover Picture: Reprogramming the Biosynthesis of Cyclodepsipeptide Synthetases to Obtain New Enniatins and Beauvericins (ChemBioChem 4/2016) 下载免费PDF全文
50.
Inside Cover: Onocerin Biosynthesis Requires Two Highly Dedicated Triterpene Cyclases in a Fern Lycopodium clavatum (ChemBioChem 4/2016) 下载免费PDF全文