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霍刘杰
  邮箱   lhuo@sdu.edu.cn 
TA的实验室:   微生物多肽类天然产物
论文

Characterization of a dehydratase and methyltransferase in the biosynthesis of a ribosomally‐synthesized and post‐translationally modified peptide in Lachnospiraceae

期刊: ChemBioChem  2019
作者: Wilfred A. Van Der Donk,Satish K. Nair,Paola Estrada,Jeella Z. Acedo,Xiling Zhao,Liujie Huo
DOI:10.1002/cbic.201900483

Heterologous expression of bacterial natural product biosynthetic pathways

The review highlights the 2013–2018 literature on the heterologous expression of bacterial natural product biosynthetic pathways and emphasises new techniques, heterologous hosts, and novel chemistry.

期刊: Natural Product Reports  2019
作者: Rolf Müller,Youming Zhang,Xiaoying Bian,Chengzhang Fu,Joachim J. Hug,Liujie Huo
DOI:10.1039/c8np00091c

Insights into AMS/PCAT transporters from biochemical and structural characterization of a double Glycine motif protease

The secretion of peptides and proteins is essential for survival and ecological adaptation of bacteria. Dual-functional ATP-binding cassette transporters export antimicrobial or quorum signaling peptides in Gram-positive bacteria. Their substrates contain a leader sequence that is excised by an N-terminal peptidase C39 domain at a double Gly motif. We characterized the protease domain (LahT150) of a transporter from a lanthipeptide biosynthetic operon in Lachnospiraceae and demonstrate that this protease can remove the leader peptide from a diverse set of peptides. The 2.0 Å resolution crystal structure of the protease domain in complex with a covalently bound leader peptide demonstrates the basis for substrate recognition across the entire class of such transporters. The structural data also provide a model for understanding the role of leader peptide recognition in the translocation cycle, and the function of degenerate, non-functional C39-like domains (CLD) in substrate recruitment in toxin exporters in Gram-negative bacteria.

期刊: eLife  2019
作者: Wilfred A. Van Der Donk,Satish K. Nair,Gonzalo Jiménez-Osés,Martin I Mclaughlin,Nuria Mazo,Liujie Huo,Shi-Hui Dong,Silvia C Bobeica
DOI:10.7554/elife.42305

Discovery of recombinases enables genome mining of cryptic biosynthetic gene clusters in Burkholderiales species

Bacterial genomes encode numerous cryptic biosynthetic gene clusters (BGCs) that represent a largely untapped source of drugs or pesticides. Mining of the cryptic products is limited by the unavailability of streamlined genetic tools in native producers. Precise genome engineering using bacteriophage recombinases is particularly useful for genome mining. However, recombinases are usually host-specific. The genome-guided discovery of novel recombinases and their transient expression could boost cryptic BGC mining. Herein, we reported a genetic system employing Red recombinases from Burkholderiales strain DSM 7029 for efficient genome engineering in several Burkholderiales species that currently lack effective genetic tools. Using specialized recombinases-assisted in situ insertion of functional promoters, we successfully mined five cryptic nonribosomal peptide synthetase/polyketide synthase BGCs, two of which were silent. Two classes of lipopeptides, glidopeptins and rhizomides, were identified through extensive spectroscopic characterization. This recombinase expression strategy offers utility within other bacteria species, allowing bioprospecting for potentially scalable discovery of novel metabolites with attractive bioactivities.

期刊: Proceedings of the National Academy of Sciences  2018
作者: Youming Zhang,Xiaoying Bian,Rolf Müller,Xiaoming Ding,Yuemao Shen,Yue-Zhong Li,Liujie Huo,Jun Fu,Jiaqi Liu,Tao Sun,Ruijuan Li,Wentao Zheng,Xiaoshu Jing,Hanna Chen,Haibo Zhou,Xue Wang
DOI:10.1073/pnas.1720941115

Synthetic biology approaches to establish a heterologous production system for coronatines

期刊: Metabolic Engineering  2017
作者: Silke C. Wenzel,Rolf Müller,Lutz Petzke,Patrick Pilak,Liujie Huo,Michael Hoffmann,Katja Gemperlein
DOI:10.1016/j.ymben.2017.09.009

Synthesis and Bioactivity of Diastereomers of the Virulence Lanthipeptide Cytolysin

期刊: Organic Letters  2016
作者: Wilfred A. Van Der Donk,Gabrielle N. Thibodeaux,Liujie Huo,Subha Mukherjee
DOI:10.1021/acs.orglett.6b03246

Structure and Substrate Recognition of the Bottromycin Maturation Enzyme BotP

期刊: ChemBioChem  2016
作者: Jesko Koehnke,Rolf Müller,Nicholas James Westwood,Jeremie Vendome,Brunello Nardone,Sebastian Adam,Liujie Huo,Greg Mann
DOI:10.1002/cbic.201600406

Discovery and Characterization of Bicereucin, an Unusual d-Amino Acid-Containing Mixed Two-Component Lantibiotic

期刊: Journal of the American Chemical Society  2016
作者: Wilfred A. Van Der Donk,Liujie Huo
DOI:10.1021/jacs.6b02513

Insights into the Biosynthesis of Duramycin

ABSTRACT Lantibiotics are ribosomally synthesized and posttranslationally modified antimicrobial peptides that are characterized by the thioether cross-linked bisamino acids lanthionine (Lan) and methyllanthionine (MeLan). Duramycin contains 19 amino acids, including one Lan and two MeLans, an unusual lysinoalanine (Lal) bridge formed from the ε-amino group of lysine 19 and a serine residue at position 6, and an erythro -3-hydroxy- l -aspartic acid at position 15. These modifications are important for the interactions of duramycin with its biological target, phosphatidylethanolamine (PE). Based on the binding affinity and specificity for PE, duramycin has been investigated as a potential therapeutic, as a molecular probe to investigate the role and localization of PE in biological systems, and to block viral entry into mammalian cells. In this study, we identified the duramycin biosynthetic gene cluster by genome sequencing of Streptomyces cinnamoneus ATCC 12686 and investigated the dur biosynthetic machinery by heterologous expression in Escherichia coli . In addition, the analog duramycin C, containing six amino acid changes compared to duramycin, was successfully generated in E. coli . The substrate recognition motif of DurX, an α-ketoglutarate/iron(II)-dependent hydroxylase that carries out the hydroxylation of aspartate 15 of the precursor peptide DurA, was also investigated using mutagenesis of the DurA peptide. Both in vivo and in vitro results demonstrated that Gly16 is important for DurX activity. IMPORTANCE Duramycin is a natural product produced by certain bacteria that binds to phosphatidylethanolamine (PE). Because PE is involved in many cellular processes, duramycin is an antibiotic that kills bacteria, but it has also been used as a molecular probe to detect PE and monitor its localization in mammalian cells and even whole organisms, and it was recently shown to display broad-spectrum inhibition of viral entry into host cells. In addition, the molecule has been evaluated as treatment for cystic fibrosis. We report here the genes that are involved in duramycin biosynthesis, and we produced duramycin by expressing those genes in Escherichia coli . We show that duramycin analogs can also be produced. The ability to access duramycin and analogs by production in E. coli opens opportunities to improve duramycin as an antibiotic, PE probe, antiviral, or cystic fibrosis therapeutic.

期刊: Applied and Environmental Microbiology  2016
作者: Wilfred A. Van Der Donk,Ming Zhao,Ayşe Ökesli,Liujie Huo
DOI:10.1128/aem.02698-16

Synthetic Biotechnology to Study and Engineer Ribosomal Bottromycin Biosynthesis

期刊: Chemistry & Biology  2012
作者: Rolf Müller,Silke C. Wenzel,Marc Stadler,Shwan Rachid,Liujie Huo
DOI:10.1016/j.chembiol.2012.08.013

Stereoselective Synthesis of Deuterium-Labeled (2S)-Cyclohexenyl Alanines, Biosynthetic Intermediates of Cinnabaramide

期刊: Organic Letters  2012
作者: Uli Kazmaier,Rolf Müller,Liujie Huo,Philipp Barbie
DOI:10.1021/ol3029548

Mining the Cinnabaramide Biosynthetic Pathway to Generate Novel Proteasome Inhibitors

期刊: ChemBioChem  2011
作者: Rolf Müller,Jens Bitzer,Bärbel Köpcke,Marc Stadler,Jennifer Herrmann,Liujie Huo,Shwan Rachid
DOI:10.1002/cbic.201100024

Unusual carbon fixation gives rise to diverse polyketide extender units

期刊: Nature Chemical Biology  2011
作者: Rolf Müller,Dirk W Heinz,Shwan Rachid,Liujie Huo,Nick Quade
DOI:10.1038/nchembio.734

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