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| 1 | The secondary metabolite bioinformatics portal: Computational tools to facilitate synthetic biology of secondary metabolite production显示文摘Natural products are among the most important sources of lead molecules for drug discovery.With the development of affordable whole-genome sequencing technologies and other‘omics tools,the field of natural products research is currently undergoing a shift in paradigms.While,for decades,mainly analytical and chemical methods gave access to this group of compounds,nowadays genomics-based methods offer complementary approaches to find,identify and characterize such molecules.This paradigm shift also resulted in a high demand for computational tools to assist researchers in their daily work.In this context,this review gives a summary of tools and databases that currently are available to mine,identify and characterize natural product biosynthesis pathways and their producers based on‘omics data.A web portal called Secondary Metabolite Bioinformatics Portal(SMBP at http://gffzz02e507a9d8884f08hok59k60fxxuw6von.ffgz.tsg.suse.edu.cn)is introduced to provide a one-stop catalog and links to these bioinformatics resources.In addition,an outlook is presented how the existing tools and those to be developed will influence synthetic biology approaches in the natural products field. | Tilmann Weber Hyun Uk Kim | 2016 | Synthetic and Systems Biotechnology2016，1，2： | 10 |
| 2 | Depiction of secondary metabolites and antifungal activity of Bacillus velezensis DTU001显示文摘For a safe and sustainable environment,effective microbes as biocontrol agents are in high demand.We have isolated a new Bacillus velezensis strain DTU001,investigated its antifungal spectrum,sequenced its genome,and uncovered the production of lipopeptides in HPLC-HRMS analysis.To test the antifungal efficacy,extracts of B.velezensis DTU001 was tested against a range of twenty human or plant pathogenic fungi.We demonstrate that inhibitory potential of B.velezensis DTU001 against selected fungi is superior in comparison to single lipopeptide,either iturin or fengycin.The isolate showed analogous biofilm formation to other closely related Bacilli.To further support the biocontrol properties of the isolate,coculture with Candida albicans demonstrated that B.velezensis DTU001 exhibited excellent antiproliferation effect against C.albicans.In summary,the described isolate is a potential antifungal agent with a broad antifungal spectrum that might assist our aims to avoid hazardous pathogenic fungi and provide alternative to toxicity caused by chemicals. | Sagarika Devi Heiko T.Kiesewalter Renato Kovacs Jens Christian Frisvad Tilmann Weber Thomas Ostenfeld Larsen Akos T.Kovacs Ling Ding | 2019 | Synthetic and Systems Biotechnology2019，4，3： | 4 |
| 3 | Reprogramming acyl carrier protein interactions of an acyl-CoA promiscuous trans-acyltransferase显示文摘 | Zhixia Ye Ewa M. Musiol Tilmann Weber Gavin J. Williams | 2014 | Chemistry & Biology2014，，： | 1 |
| 4 | Molecular Analysis of the Kirromycin Biosynthetic Gene Cluster Revealed β-Alanine as Precursor of the Pyridone Moiety显示文摘 | Tilmann Weber Kristina Juliane Laiple Eva Karoline Pross Adriana Textor Stephanie Grond Katrin Welzel Stefan Pelzer Andreas Vente Wolfgang Wohlleben | 2008 | Chemistry & Biology2008，，： | 1 |
| 5 | Designing sgRNAs for CRISPR-BEST base editing applications with CRISPyweb 2.0显示文摘CRISPR/Cas9 systems are an established tool in genome engineering.As double strand breaks caused by the standard Cas9-based knock-out techniques can be problematic in some organisms,new systems were developed that can efficiently create knock-outs without causing double strand breaks to elegantly sidestep these issues.The recently published CRISPR-BEST base editor system for actinobacteria is built around a C to T or A to G base exchange.These base editing systems however require additional constraints to be considered for designing the sgRNAs.Here,we present an updated version of the interactive CRISPy-web single guide RNA design tool http://gffzz2b22c00a04674870sok59k60fxxuw6von.ffgz.tsg.suse.edu.cn/that was built to support“classical”CRISPR and now also CRISPRBEST workflows. | Kai Blin Simon Shaw Yaojun Tong Tilmann Weber | 2020 | Synthetic and Systems Biotechnology2020，5，2： | 0 |
| 6 | Programmable polyketide biosynthesis platform for production of aromatic compounds in yeast显示文摘To accelerate the shift to bio-based production and overcome complicated functional implementation of natural and artificial biosynthetic pathways to industry relevant organisms,development of new,versatile,bio-based production platforms is required.Here we present a novel yeast-based platform for biosynthesis of bacterial aromatic polyketides.The platform is based on a synthetic polyketide synthase system enabling a first demonstration of bacterial aromatic polyketide biosynthesis in a eukaryotic host. | Tadas Jakočiūnas Andreas K.Klitgaard Eftychia Eva Kontou Julie Bang Nielsen Emil Thomsen David Romero-Suarez Kai Blin Christopher J.Petzold Jennifer W.Gin Yaojun Tong Charlotte Held Gotfredsen Pep Charusanti Rasmus J.N.Frandsen Tilmann Weber Sang Yup Lee Michael K.Jensen Jay D.Keasling | 2020 | Synthetic and Systems Biotechnology2020，5，1： | 0 |
| 7 | Identification and heterologous expression of the globomycin biosynthetic gene cluster显示文摘Globomycin is a cyclic lipodepsipeptide originally isolated from several Streptomyces species which displays strong and selective antibacterial activity against Gram-negative pathogens.Its mode of action is based on the competitive inhibition of the lipoprotein signal peptidase II(LspA),which is absent in eukaryotes and considered an attractive target for the development of new antibiotics.Despite its interesting biological properties,the gene cluster encoding its biosynthesis has not yet been identified.In this study we employed a genome-mining approach in the globomycin-producing Streptomyces sp.CA-278952 to identify a candidate gene cluster responsible for its biosynthesis.A null mutant was constructed using CRISPR base editing where production was abolished,strongly suggesting its involvement in the biosynthesis.The putative gene cluster was then cloned and heterologously expressed in Streptomyces albus J1074 and Streptomyces coelicolor M1146,therefore unambigu-ously linking globomycin and its biosynthetic gene cluster.Our work paves the way for the biosynthesis of new globomycin derivatives with improved pharmacological properties. | Daniel Oves-Costales Tetiana Gren Eva Baggesgaard Sterndorff Jesús Martín Francisco Javier Ortiz-Lopez Tue S.Jørgensen Xinglin Jiang Fernando Roman-Hurtado Fernando Reyes Olga Genilloud Tilmann Weber | 2023 | Synthetic and Systems Biotechnology2023，8，2： | 0 |
| 8 | Discovery of gargantulides B and C,new 52-membered macrolactones from Amycolatopsis sp.Complete absolute stereochemistry of the gargantulide family显示文摘Gargantulides B and C,two new and highly complex 52-membered glycosylated macrolactones,were isolated from Amycolatopsis sp.strain CA-230715 during an antibacterial screening campaign.The structures of these giant macrolides were elucidated by 2D NMR spectroscopy and shown to be related to gargantulide A,although containing additional β-glucopyranose and/orα-arabinofuranose monosaccharides separately attached to their backbones.Genome sequencing allowed the identification of a strikingly large 216 kbp biosynthetic gene cluster,among the largest type Ⅰ PKS clusters described so far,and the proposal of a previously unreported biosynthetic pathway for gargantulides A-C.The absolute configurations of gargantulides B and C were assigned based on a combination of NMR and bioinformatics analysis of ketoreductase and enoylreductase domains within the multimodular type Ⅰ PKS.In addition,the absolute stereochemistry of gargantulide A has now been revised and completed.Gargantulides B and C display potent antibacterial activity against a set of drug-resistant Gram-positive bacteria and moderate activity against the clinically relevant Gram-negative pathogen Acinetobacter baumannii. | Daniel Carretero-Molina Francisco Javier Ortiz-López Tetiana Gren Daniel Oves-Costales Jesús Martín Fernando Román-Hurtado Tue Sparholt Jorgensen Mercedes de la Cruz Caridad Díaz Francisca Vicente Kai Blin Fernando Reyes Tilmann Weber Olga Genilloud | 2022 | Organic Chemistry Frontiers2022，9，2： | 0 |
| 9 | Pangenome analysis of Enterobacteria reveals richness of secondary metabolite gene clusters and their associated gene sets显示文摘In silico genome mining provides easy access to secondary metabolite biosynthetic gene clusters(BGCs)encoding the biosynthesis of many bioactive compounds,which are the basis for many important drugs used in human medicine.However,the association between BGCs and other functions encoded in the genomes of producers have remained elusive.Here,we present a systems biology workflow that integrates genome mining with a detailed pangenome analysis for detecting genes associated with a particular BGC.We analyzed 3,889 enterobacterial genomes and found 13,266 BGCs,represented by 252 distinct BGC families and 347 additional singletons.A pangenome analysis revealed 88 genes putatively associated with a specific BGC coding for the colon cancer-related colibactin that code for diverse metabolic and regulatory functions.The presented workflow opens up the possibility to discover novel secondary metabolites,better understand their physiological roles,and provides a guide to identify and analyze BGC associated gene sets. | Omkar S.Mohite Colton J.Lloyd Jonathan M.Monk Tilmann Weber Bernhard O.Palsson | 2022 | Synthetic and Systems Biotechnology2022，7，3： | 0 |
| 10 | Introduction to the Special Issue “Bioinformatic tools and approaches for Synthetic Biology of natural products”显示文摘Microorganisms are the major source for the identification of novel bioactive natural products,which may serve as future lead molecules for drug development to treat infectious and other diseases.However,the research efforts to find such molecules have been hampered by high re-discovery rates of known biomolecules and a lack of new innovative screening technologies resulting in reduced screening efforts by large parts of the pharmaceutical industry.With recent advances in whole-genome sequencing technologies,mass spectrometry,cheminformatics and Synthetic Biology,new technologies are now available that could become game-changers in the field.All these technologies require strong computational efforts to analyze and mine the large datasets,and/or design and optimize new pathways for Synthetic Biology applications. | Tilmann Weber | 2016 | Synthetic and Systems Biotechnology2016，1，2： | 0 |
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