Article
Plant Sciences
Hannah P. McDonald, Abigail Alford, Rebecca Devine, Edward S. Hems, Sergey A. Nepogodiev, Corinne J. Arnold, Martin Rejzek, Anna Stanley-Smith, Neil A. Holmes, Matthew I. Hutchings, Barrie Wilkinson
Summary: Formicamycins and their biosynthetic intermediates thefasamycins are polyketide antibiotics produced by Streptomyces formicae KY5 through the for biosynthetic gene cluster. Heterologous expression of the for gene cluster in Streptomyces coelicolor M1146 and Saccharopolyspora erythraea & UDelta;ery led to the identification of eight new glycosylated fasamycins, modified at different phenolic groups with either a monosaccharide or a disaccharide. However, these glycosylated congeners showed no antibacterial activity in minimal inhibitory screening assays compared to the respective aglycones.
JOURNAL OF NATURAL PRODUCTS
(2023)
Article
Multidisciplinary Sciences
Jasmin Hafner, James Payne, Homa MohammadiPeyhani, Vassily Hatzimanikatis, Christina Smolke
Summary: This study introduces a computational workflow to systematically screen the biochemical vicinity of plant natural product (PNP) biosynthetic pathways for pharmaceutical compounds. Applying the workflow to noscapine biosynthesis pathway, pathways and enzyme candidates for the production of (S)-tetrahydropalmatine were identified, showcasing the value of cheminformatic tools in predicting reactions, pathways, and enzymes in synthetic biology.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Camila T. M. N. Porfirio, Pedro F. N. Souza, Marcio V. Ramos, Francisco A. P. Campos, Samuel F. Freitas, Joao P. B. Oliveira, Gilvan P. Furtado, Jose S. S. Barbosa, Thalia L. Frota, Celso S. Nagano, Rodolpho G. G. Silva, Ghulam Hussain, Cleverson D. T. Freitas
Summary: This study partially characterized three serine carboxypeptidases from Nepenthes mirabilis and further analyzed one peptidase in terms of its allergenic potential. The results showed that these enzymes have similar structures and mechanisms to other plant serine peptidases.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Article
Biochemistry & Molecular Biology
Zhilei Li, Lang He, Xia Wang, Qingwen Huo, Guosong Zheng, Dekun Kong, Yinhua Lu, Haiyang Xia, Guoqing Niu
Summary: Sideromycins are a unique subset of siderophores that combine a siderophore and an antimicrobial agent. This study deciphered the biosynthetic pathway of the ferrichrome-type siderophore in Streptomyces sp. ATCC 700974 and identified the involved genes. The findings provide important insights into the synthesis of albomycin and the role of multiple siderophores in Streptomyces sp. ATCC 700974.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Microbiology
Weiyi She, Wenkang Ye, Aifang Cheng, Xin Liu, Jianwei Tang, Yi Lan, Feng Chen, Pei-Yuan Qian
Summary: Novel albofungin derivatives discovered from Streptomyces chrestomyceticus exhibit potent activities against pathogens and cancer cells, making them potential candidates for the development of antibiotics and antitumor drugs.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Biotechnology & Applied Microbiology
Zhihui Chen, Yongzhi He, Xinyu Wu, Li Wang, Zhiyang Dong, Xiuzhen Chen
Summary: Through genetic engineering, genes from Trichoderma reesei and N. crassa were successfully transferred to E. coli, enabling efficient synthesis of ergothioneine. The combination of genes from T. reesei showed the best synthesis efficiency, reaching up to 4.34 g/L per liter.
MICROBIAL CELL FACTORIES
(2022)
Article
Biotechnology & Applied Microbiology
Hong Li, Yuanyuan Pan, Gang Liu
Summary: By cloning and amplifying the spinosad BGC in Streptomyces coelicolor M1146 using Cas9-Assisted Targeting of Chromosome segments and a DNA amplification system, the production of spinosad was significantly increased. Further enhancement to nearly 2000 µg/L was achieved by dynamically regulating intracellular triacylglycerol degradation. Tandem amplification of the targeted gene cluster is shown to be effective and simple for increasing the production of valuable NPs.
MICROBIAL BIOTECHNOLOGY
(2022)
Article
Multidisciplinary Sciences
Natalie S. Kolber, Ranan Fattal, Sinisa Bratulic, Gavriela D. Carver, Ahmed H. Badran
Summary: The study explores the potential of engineering heterologous ribosomes in living cells, discovering that optimized rRNA processing and supplementation with cognate r-proteins can enhance their function. It also notes reduced subunit exchange with host ribosomes for some heterologous ribosomes. This work provides a general framework for heterologous ribosome engineering and expands the use of heterologous parts in synthetic biology.
NATURE COMMUNICATIONS
(2021)
Article
Biotechnology & Applied Microbiology
Takuya Hashimoto, Junko Hashimoto, Noritaka Kagaya, Takehiro Nishimura, Hikaru Suenaga, Makoto Nishiyama, Tomohisa Kuzuyama, Kazuo Shin-ya
Summary: A novel biosynthetic gene cluster containing trans-AT type PKS genes was identified from Streptomyces versipellis 4083-SVS6, leading to the production of a novel polyene compound, JBIR-159, through heterologous expression in Streptomyces lividans TK23.
JOURNAL OF ANTIBIOTICS
(2021)
Article
Biology
Muhammad Mustafa, Liaqat Ali, Waqar Islam, Ali Noman, Chengzeng Zhou, Linsong Shen, Taoting Zhu, Liu Can, Omaima Nasif, Kristina Gasparovic, Farooq Latif, Jiangtao Gao
Summary: This study focuses on the expression and purification of a thermostable glycoside hydrolase enzyme from the hyperthermophile Thermotoga maritima, which shows high stability in extreme environments such as acidic pH and high temperatures. The introduction of Ca2+ and Mn2+ further enhances the activity of the recombinant enzyme, suggesting its potential for industrial applications in hyperthermic conditions.
SAUDI JOURNAL OF BIOLOGICAL SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Rebecca Devine, Hannah P. McDonald, Zhiwei Qin, Corinne J. Arnold, Katie Noble, Govind Chandra, Barrie Wilkinson, Matthew Hutchings
Summary: The study identified promising antibiotics formicamycins, and showed that understanding the regulation of the biosynthetic gene cluster can increase production levels and induce the production of additional congeners.
CELL CHEMICAL BIOLOGY
(2021)
Article
Plant Sciences
Rui Li, Ya Yang, Hanping Cao, Xiang Peng, Qin Yu, Linshen He, Ji Chen, Lien Xiang, Wanhong Liu
Summary: Heavy metal pollution in the soil poses a serious threat to both crop growth and human health. In this study, a new metallothionein encoding gene, NtMT2F, was cloned from Cd-hyperaccumulator tobacco and expressed in E. coli and A. thaliana to examine its biological function. The results showed that NtMT2F effectively enhanced resistance to heavy metal stress, particularly Cd, in both E. coli and transgenic A. thaliana. The findings suggest that NtMT2F could be a promising protein candidate for phytoremediation of heavy metal-contaminated environments.
PLANT PHYSIOLOGY AND BIOCHEMISTRY
(2023)
Article
Biotechnology & Applied Microbiology
Zhen-Yang Shen, Yi-Feng Wang, Ying Wang, Zhi-Qiang Liu, Yu-Guo Zheng
Summary: This study investigates the metabolic response and crucial genes in the biosynthetic pathway of iota-methionine. The relationship between different pathways and their controlling forces on metabolic flux are also examined. The findings provide insights into the biosynthesis of iota-methionine and offer a new research method for synthesizing other metabolic products in multilevel regulated and multibranched biosynthetic pathways.
JOURNAL OF BIOSCIENCE AND BIOENGINEERING
(2023)
Article
Biotechnology & Applied Microbiology
Pei-Pei Wei, Fu-Cheng Zhu, Cun-Wu Chen, Guo-Si Li
Summary: By introducing a heterologous biotin synthetic pathway and increasing the supply of precursor pimeloyl-CoA and cofactor SAM, biotin production in E. coli can be significantly enhanced. This approach led to a 121-fold increase in biotin production, reaching 92.6 mg/L in a shake flask and 208.7 mg/L in a fed-batch fermenter.
BIOTECHNOLOGY LETTERS
(2021)
Article
Plant Sciences
Xingxing Wei, Tsz Ki Chan, Che Tung Derek Kong, Yudai Matsuda
Summary: The biosynthetic gene cluster for the cyclic heptapeptides unguisins A and B, which contain the neurotransmitter gamma-aminobutyric acid (GABA), was discovered in the fungus Aspergillus violaceofuscus CBS 115571. Enzymatic reactions and gene deletion experiments showed that the unguisin pathway involves the alanine racemase UngC to produce D-alanine, which is then utilized by the first adenylation domain of the nonribosomal peptide synthetase UngA. Surprisingly, the hydrolase UngD was found to convert unguisins into previously unknown linear peptides. Heterologous production of these peptides was achieved in Aspergillus oryzae, and genome mining revealed new unguisin variants, each containing a (2R,3R)-beta-methylphenylalanine residue.
JOURNAL OF NATURAL PRODUCTS
(2023)
Article
Chemistry, Multidisciplinary
Luka Raguz, Chia-Chi Peng, Marcel Kaiser, Helmar Gorls, Christine Beemelmanns
Summary: A synthetic approach towards the sphingofungin family was reported, yielding eight derivatives tested for antifungal, cell-proliferative, and antiparasitic activities, revealing structure-activity relations.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Che-Sheng Hsu, Carlos R. Goncalves, Veronica Tona, Amandine Pons, Marcel Kaiser, Nuno Maulide
Summary: The article presents a method of synthesizing amine compounds using highly electron-deficient iminium ions and highlights its broad applicability through a specific case study.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Nadya Abbood, Tien Duy Vo, Jonas Watzel, Kenan A. J. Bozhueyuek, Helge B. Bode
Summary: Bacterial natural products, especially non-ribosomally synthesized peptides, are structurally diverse and have a wide range of pharmaceutical bioactivities. Traditional natural product research is inefficient and time-consuming, while combinatorial chemistry can produce new molecules quickly but is limited by the biologically relevant chemical space. High throughput generation of new natural products offers a new approach to drug discovery.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Agriculture, Multidisciplinary
Desalegne Abebew, Fatemeh S. Sayedain, Edna Bode, Helge B. Bode
Summary: This study has identified new nematicidal natural products from Xenorhabdus bacteria, which can provide templates for discovering environmentally safe alternatives to commercially available nematicides. Among the tested natural products, fabclavines, rhabdopeptides, and xenocoumacins showed high toxicity to nematodes.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Sabina Beilstein, Radhia El Phil, Suzanne Sherihan Sahraoui, Leonardo Scapozza, Marcel Kaiser, Pascal Maser
Summary: This article discusses the experimental methods and strategies for selecting drug-resistant parasites, using African trypanosomes as an example. Researchers need to consider factors such as the environmental conditions, life stages, and pressure for selecting drug resistance, while taking into account the laboratory settings.
Article
Biochemistry & Molecular Biology
Ozlem Sevik Kilicaslan, Sylvian Cretton, Luis Quiros-Guerrero, Merveilles A. Bella, Marcel Kaiser, Pascal Maeser, Joseph T. Ndongo, Muriel Cuendet
Summary: This study isolated and identified 16 compounds from P. bicarpellata extracts, including two previously unreported compounds. The absolute configurations of these compounds were determined through analysis of experimental and calculated data. The extracts and compounds were evaluated for their antiprotozoal activity, with tubotaiwine displaying the most significant antiplasmodial activity.
Article
Chemistry, Organic
Blaise Kimbadi Lombe, Lea Winand, Jan Diettrich, Melanie Tobermann, Wolf Hiller, Marcel Kaiser, Markus Nett
Summary: In this study, we report the discovery of massinidine, an aguanidine alkaloid with antiplasmodial activity, from bacteria of the genus Massilia. The biosynthetic genes of massinidine were identified and validated through heterologous expression. Bioinformatic analysis reveals the widespread potential for massinidine biosynthesis in various proteobacteria.
Article
Biochemistry & Molecular Biology
Yi-Ming Shi, Merle Hirschmann, Yan-Ni Shi, Helge B. Bode
Summary: This study characterizes the biosynthetic logic of Piscibactins and photoxenobactins, metallophores and virulence factors. It shows that the biosynthesis involves heterocyclization domains with different catalytic efficiencies and putative bond cleavage off-loading manners. Spontaneous conversions of the biosynthetic end product also contribute to the production of other products.
ACS CHEMICAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Clemens Hinteregger, Johanna Dolensky, Werner Seebacher, Robert Saf, Pascal Maeser, Marcel Kaiser, Robert Weis
Summary: 2,4-Diaminopyrimidines and (dialkylamino)azabicyclo-nonanes have activity against protozoan parasites. A series of fused hybrids were synthesized and tested in vitro against malaria tropica and sleeping sickness pathogens. The activities and selectivities of compounds strongly depended on the substitution pattern of both ring systems as well as the position of the nitrogen atom in the bicycles.
Article
Chemistry, Multidisciplinary
Werner Seebacher, Marcel Kaiser, Pascal Maeser, Robert Saf, Eva-Maria Pferschy-Wenzig, Robert Weis
Summary: Several 1-benzyl and 1,3-dibenzyl derivatives of tetrahydropyridinylidene salts with varying electron withdrawing substituents at the aromatic residues have been synthesized and investigated for their biological activities and cytotoxicity. Characterization of these compounds was carried out using FT-IR, HRMS and NMR spectroscopy.
MONATSHEFTE FUR CHEMIE
(2023)
Article
Chemistry, Organic
Qiaoqiao Tao, Yining Sang, Tao Han, Hongling Zhou, Peng Zhang, Xiaofeng Cai
Summary: Five new uncommon 20-nor-isopimarane diterpenoids, aspewentins N-R (1-5), and three related known congeners (6-8), along with an isopimarane diterpenoid, sphaeropsidin C (9), were isolated from a Coptis chinensis Franch. rhizosphere soil-derived fungal strain, Aspergillus sp. WT03. The structures of compounds 1-9 were characterized based on the comprehensive analysis of the spectroscopic data, and their absolute configurations were elucidated by single crystal X-ray diffraction and time-dependent density functional theory (TDDFT)-ECD calculations. Compounds 1-5 represent rare examples of 20-nor-isopimarane analogues featuring a 1,2,3,4-tetrahydronaphthalene and 3,4-dihydronaphthalen-1(2H)-one moiety. The biosynthetic pathway of these diterpenoids was also proposed. Additionally, compounds 1, 3 and 4 showed moderate cytotoxic activity against MCF-7, A549 and HT-29 cell lines.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2023)
Article
Biochemical Research Methods
Xiaofeng Cai, Lei Zhao, Helge B. Bode
Summary: The nonribosomal peptide synthetases (NRPSs) derived from entomopathogenic Xenorhabdus and Photorhabdus bacteria, known as Rhabdopeptide/xenortide-like peptide (RXP), often produce a diverse range of peptides due to promiscuous docking domains (DDs) that mediate interaction between different NRPS subunits. This study demonstrates the generation of specific RXPs by exchanging adenylation/methyltransferase (A-MT) domains in two RXP-NRPS systems with specific DDs, followed by heterologous expression in Escherichia coli. Furthermore, the study suggests that NRPS subunit interaction is not solely dependent on DDs, but also partially on A domains.
ACS SYNTHETIC BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Srinivasa P. S. Rao, Matthew K. Gould, Jonas Noeske, Manuel Saldivia, Rajiv S. Jumani, Pearly S. Ng, Olivier Rene, Yen-Liang Chen, Marcel Kaiser, Ryan Ritchie, Amanda Fortes Francisco, Nila Johnson, Debjani Patra, Harry Cheung, Colin Deniston, Andreas D. Schenk, Wilian A. Cortopassi, Remo S. Schmidt, Natalie Wiedemar, Bryanna Thomas, Rima Palkar, Nahdiyah A. Ghafar, Vanessa Manoharan, Catherine Luu, Jonathan E. Gable, Kah Fei Wan, Elmarie Myburgh, Jeremy C. Mottram, Whitney Barnes, John Walker, Charles Wartchow, Natasha Aziz, Colin Osborne, Juergen Wagner, Christopher Sarko, John M. Kelly, Ujjini H. Manjunatha, Pascal Maeser, Jan Jiricek, Suresh B. Lakshminarayana, Michael P. Barrett, Thierry T. Diagana
Summary: Millions of people in Latin America and sub-Saharan Africa are at risk of trypanosomatid infections. Researchers have identified a class of cyanotriazoles (CTs) that have potent trypanocidal activity and can potentially be used for the treatment of Chagas disease and human African trypanosomiasis. These CT compounds act by selectively and irreversibly inhibiting trypanosomal topoisomerase II and stabilizing DNA:enzyme cleavage complexes.
Article
Biochemical Research Methods
Nadya Abbood, Juliana Effert, Kenan A. J. Bozhueyuek, Helge B. Bode
Summary: This study introduced a synthetic variant of nonribosomal peptide synthetase, called type S NRPS, which simplifies the engineering process and enables high-throughput generation of nonribosomal peptide libraries. Through optimization strategies, significant improvements in production yields were achieved, demonstrating the potential of engineering bacterial biosynthetic assembly lines for artificial nonribosomal peptide production.
ACS SYNTHETIC BIOLOGY
(2023)
Article
Mathematical & Computational Biology
Arnaud Gaudry, Florian Huber, Louis-Felix Nothias, Sylvian Cretton, Marcel Kaiser, Jean-Luc Wolfender, Pierre-Marie Allard
Summary: In natural products research, it is challenging to compare samples from different batches due to experimental variation. Researchers have introduced a new method called MEMO-MS2 BasEd SaMple VectOrization, which allows clustering of chemodiverse samples based on their LC-MS/MS profiles without considering retention time. This method provides similar clustering performance as state-of-the-art metrics, but without the need for a prior feature alignment step and with shorter computational time. It enables the comparison of vast ensembles of samples analyzed over long periods of time and on different chromatographic or mass spectrometry platforms, expanding the scope of large-scale comparative analysis.
FRONTIERS IN BIOINFORMATICS
(2022)
