{"title":"Correction to: Characterization and catalytic investigation of fungal single-module nonribosomal peptide synthetase in terpene-amino acid meroterpenoid biosynthesis.","authors":"","doi":"10.1093/jimb/kuae002","DOIUrl":"10.1093/jimb/kuae002","url":null,"abstract":"","PeriodicalId":16092,"journal":{"name":"Journal of Industrial Microbiology & Biotechnology","volume":"51 ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10845890/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139485729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Elizabeth Bodie, Zhongqiang Chen, Kirstin Crotty, Cherry Lin, Chuanbin Liu, Sergio Sunux, Michael Ward
{"title":"Evolution and screening of Trichoderma reesei mutants for secreted protein production at elevated temperature.","authors":"Elizabeth Bodie, Zhongqiang Chen, Kirstin Crotty, Cherry Lin, Chuanbin Liu, Sergio Sunux, Michael Ward","doi":"10.1093/jimb/kuae038","DOIUrl":"10.1093/jimb/kuae038","url":null,"abstract":"<p><p>The filamentous fungus Trichoderma reesei is a mesophilic ascomycete commercially used to produce industrial enzymes for a variety of applications. Strain improvement efforts over many years have resulted not only in more productive hosts, but also in undesirable traits such as the need for lower temperatures to achieve maximum protein secretion rates. Lower fermentation temperatures increase the need for cooling resulting in higher manufacturing costs. We used a droplet-based evolution strategy to increase the protein secretion temperature of a highly productive T. reesei whole cellulase strain from 25°C to 28°C by first isolating an improved mutant and subsequently tracing the causative high-temperature mutation to one gene designated gef1. An industrial host with a gef1 deletion was found to be capable of improved productivity at higher temperature under industrially relevant fermentation conditions.</p><p><strong>One-sentence summary: </strong>High-temperature droplet-based evolution resulted in the identification of a mutation in Trichoderma reesei gef1 enabling high productivity at elevated temperatures.</p>","PeriodicalId":16092,"journal":{"name":"Journal of Industrial Microbiology & Biotechnology","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11566232/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142467553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Phytopathological management through bacteriophages: enhancing food security amidst climate change.","authors":"Ihtisham Ul Haq, Mehtab Khan, Imran Khan","doi":"10.1093/jimb/kuae031","DOIUrl":"10.1093/jimb/kuae031","url":null,"abstract":"<p><p>The increasing global population and climate change pose significant challenges to agriculture, particularly in managing plant diseases caused by phytopathogens. Traditional methods, including chemical pesticides and antibiotics, have become less effective due to pathogen resistance and environmental concerns. Phage therapy emerges as a promising alternative, offering a sustainable and precise approach to controlling plant bacterial diseases without harming beneficial soil microorganisms. This review explores the potential of bacteriophages as biocontrol agents, highlighting their specificity, rapid multiplication, and minimal environmental impact. We discuss the historical context, current applications, and prospects of phage therapy in agriculture, emphasizing its role in enhancing crop yield and quality. Additionally, the paper examines the integration of phage therapy with modern agricultural practices and the development phage cocktails and genetically engineered phages to combat resistant pathogens. The findings suggest that phage therapy could revolutionize phytopathological management, contributing to global food security and sustainable agricultural practices.</p><p><strong>One-sentence summary: </strong>The burden of plant diseases and phage-based phytopathological treatment.</p>","PeriodicalId":16092,"journal":{"name":"Journal of Industrial Microbiology & Biotechnology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11388930/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142108120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ji Hyeon Im, Seoyoung Oh, Eun Seo Bae, Soohyun Um, Sang Kook Lee, Yeon Hee Ban, Dong-Chan Oh
{"title":"Discovery and Structure Elucidation of Glycosyl and 5-Hydroxy Migrastatins from Dung Beetle Gut Kitasatospora sp.","authors":"Ji Hyeon Im, Seoyoung Oh, Eun Seo Bae, Soohyun Um, Sang Kook Lee, Yeon Hee Ban, Dong-Chan Oh","doi":"10.1093/jimb/kuad046","DOIUrl":"https://doi.org/10.1093/jimb/kuad046","url":null,"abstract":"Two new macrocyclic secondary metabolites, glycosyl-migrastatin (1) and 5-hydroxy-migrastatin (2), were isolated from a gut bacterium Kitasatospora sp. JL24 in dung beetle Onthophagus lenzii. Based on a comprehensive analysis of the NMR, MS, and UV spectroscopic data, the planar structures of 1 and 2 were successfully identified as new candidates for migrastatin. Compound 1 was the first glycosylated member of the migrastatin family. The absolute configuration of the sugar moiety was determined to be d-glucose through the analysis of coupling constants and ROESY correlations, followed by chromatographic chemical derivatization and comparison with authentic d- and l-glucose. Compound 2, identified as 5-hydroxy-migrastatin possessing an additional hydroxy group with a previously unreported chiral center, was assigned using Mosher's method through 19F NMR chemical shifts and confirmed with the modified Mosher's method. Genomic analysis of Kitasatospora sp. strain JL24 revealed a putative biosynthetic pathway involving an acyltransferase-less type I polyketide synthase biosynthetic gene cluster.","PeriodicalId":16092,"journal":{"name":"Journal of Industrial Microbiology & Biotechnology","volume":"1 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138686947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cory B Jenkinson, Adam R Podgorny, Cuncong Zhong, Berl R Oakley
{"title":"Computer-Aided, Resistance Gene-Guided Genome Mining for Proteasome and HMG-CoA Reductase Inhibitors","authors":"Cory B Jenkinson, Adam R Podgorny, Cuncong Zhong, Berl R Oakley","doi":"10.1093/jimb/kuad045","DOIUrl":"https://doi.org/10.1093/jimb/kuad045","url":null,"abstract":"Secondary metabolites (SMs) are biologically active small molecules, many of which are medically valuable. Fungal genomes contain vast numbers of SM biosynthetic gene clusters (BGCs) with unknown products, suggesting that huge numbers of valuable SMs remain to be discovered. It is challenging, however, to identify SM BGCs, among the millions present in fungi, that produce useful compounds. One solution is resistance gene-guided genome mining, which takes advantage of the fact that some BGCs contain a gene encoding a resistant version of the protein targeted by the compound produced by the BGC. The bioinformatic signature of such BGCs is that they contain an allele of an essential gene with no SM biosynthetic function, and there is a second allele elsewhere in the genome. We have developed a computer-assisted approach to resistance gene-guided genome mining that allows users to query large databases for BGCs that putatively make compounds that have targets of therapeutic interest. Working with the MycoCosm genome database, we have applied this approach to look for SM BGCs that target the proteasome β6 subunit, the target of the proteasome inhibitor fellutamide B, or HMG-CoA reductase, the target of cholesterol reducing therapeutics such as lovastatin. Our approach proved effective, finding known fellutamide and lovastatin BGCs as well as fellutamide- and lovastatin-related BGCs with variations in the SM genes that suggest they may produce structural variants of fellutamides and lovastatin. Gratifyingly, we also found BGCs that are not closely related to lovastatin BGCs but putatively produce novel HMG-CoA reductase inhibitors.","PeriodicalId":16092,"journal":{"name":"Journal of Industrial Microbiology & Biotechnology","volume":"11 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138554763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Correction to: CRISPRi screen for enhancing heterologous α-amylase yield in Bacillus subtilis.","authors":"","doi":"10.1093/jimb/kuad003","DOIUrl":"https://doi.org/10.1093/jimb/kuad003","url":null,"abstract":"Department of Veterinary and Animal Sciences, University of Copenhagen, 1870 Frederiksberg, Denmark 2 Section for Computational and RNA Biology, Department of Biology, University of Copenhagen, 2200 Copenhagen, Denmark” instead of: “1 Center for non-coding RNA in Technology and Health, Department of Veterinary and Animal Sciences, University of Copenhagen, 1172 Copenhagen, Denmark 2 Section for Computational and RNA Biology, Department of Biology, University of Copenhagen, 1172 Copenhagen, Denmark”. This is a correction to: Adrian Sven Geissler, Annaleigh Ohrt Fehler, Line Dahl Poulsen, Enrique González-Tortuero, Thomas Beuchert Kallehauge, Ferhat Alkan, Christian Anthon, Stefan Ernst Seemann, Michael Dolberg Rasmussen, Anne Breüner, Carsten Hjort, Jeppe Vinther, Jan Gorodkin, CRISPRi screen for enhancing heterologous α-amylase yield in Bacillus subtilis , Journal of Industrial Microbiology and Biotechnology , kuac028, https://doi.org/ 10.1093/jimb/kuac028","PeriodicalId":16092,"journal":{"name":"Journal of Industrial Microbiology & Biotechnology","volume":"50 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10124125/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9702429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xintong Xi, Litao Hu, Hao Huang, Yang Wang, Ruirui Xu, Guocheng Du, Jian Chen, Zhen Kang
{"title":"Improvement of the stability and catalytic efficiency of heparan sulfate N-sulfotransferase for preparing N-sulfated heparosan.","authors":"Xintong Xi, Litao Hu, Hao Huang, Yang Wang, Ruirui Xu, Guocheng Du, Jian Chen, Zhen Kang","doi":"10.1093/jimb/kuad012","DOIUrl":"10.1093/jimb/kuad012","url":null,"abstract":"<p><p>The chemo-enzymatic and enzymatic synthesis of heparan sulfate and heparin are considered as an attractive alternative to the extraction of heparin from animal tissues. Sulfation of the hydroxyl group at position 2 of the deacetylated glucosamine is a prerequisite for subsequent enzymatic modifications. In this study, multiple strategies, including truncation mutagenesis based on B-factor values, site-directed mutagenesis guided by multiple sequence alignment, and structural analysis were performed to improve the stability and activity of human N-sulfotransferase. Eventually, a combined variant Mut02 (MBP-hNST-NΔ599-602/S637P/S741P/E839P/L842P/K779N/R782V) was successfully constructed, whose half-life at 37°C and catalytic activity were increased by 105-fold and 1.35-fold, respectively. After efficient overexpression using the Escherichia coli expression system, the variant Mut02 was applied to N-sulfation of the chemically deacetylated heparosan. The N-sulfation content reached around 82.87% which was nearly 1.88-fold higher than that of the wild-type. The variant Mut02 with high stability and catalytic efficiency has great potential for heparin biomanufacturing.</p>","PeriodicalId":16092,"journal":{"name":"Journal of Industrial Microbiology & Biotechnology","volume":"50 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2023-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/21/ec/kuad012.PMC10291996.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9706234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Characterization and catalytic investigation of fungal single-module nonribosomal peptide synthetase in terpene-amino acid meroterpenoid biosynthesis.","authors":"Cheng-Chung Tseng, Li-Xun Chen, Chi-Fang Lee, Zhijay Tu, Chun-Hung Lin, Hsiao-Ching Lin","doi":"10.1093/jimb/kuad043","DOIUrl":"10.1093/jimb/kuad043","url":null,"abstract":"<p><p>Hybrid natural products are compounds that originate from diverse biosynthetic pathways and undergo a conjugation process, which enables them to expand their chemical diversity and biological functionality. Terpene-amino acid meroterpenoids have garnered increasing attention in recent years, driven by the discovery of noteworthy examples such as the anthelmintic CJ-12662, the insecticidal paeciloxazine, and aculene A (1). In the biosynthesis of terpene-amino acid natural products, single-module nonribosomal peptide synthetases (NRPSs) have been identified to be involved in the esterification step, catalyzing the fusion of modified terpene and amino acid components. Despite prior investigations into these NRPSs through gene deletion or in vivo experiments, the enzymatic basis and mechanistic insights underlying this family of single-module NRPSs remain unclear. In this study, we performed biochemical characterization of AneB by in vitro characterization, molecular docking, and site-directed mutagenesis. The enzyme reaction analyses, performed with L-proline and daucane/nordaucane sesquiterpene substrates, revealed that AneB specifically esterifies the C10-OH of aculenes with L-proline. Notably, in contrast to ThmA in CJ-12662 biosynthesis, which exclusively recognizes oxygenated amorpha-4,11-diene sesquiterpenes for L-tryptophan transfer, AneB demonstrates broad substrate selectivity, including oxygenated amorpha-4,11-diene and 2-phenylethanol, resulting in the production of diverse unnatural prolyl compounds. Furthermore, site-directed mutagenesis experiments indicated the involvement of H794 and D798 in the esterification catalyzed by AneB. Lastly, domain swapping between AneB and ThmA unveiled that the A‒T domains of ThmA can be effectively harnessed by the C domain of AneB for L-tryptophan transfer, thus highlighting the potential of the C domain of AneB for generating various terpene-amino acid meroterpenoid derivatives.</p><p><strong>One-sentence summary: </strong>The enzymatic basis and mechanistic insights into AneB, a single-module NRPS, highlight its capacity to generate various terpene-amino acid meroterpenoid derivatives.</p>","PeriodicalId":16092,"journal":{"name":"Journal of Industrial Microbiology & Biotechnology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10720950/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138482450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Eric Abbate, Jennifer Andrion, Amanda Apel, Matthew Biggs, Julie Chaves, Kristi Cheung, Anthony Ciesla, Alia Clark-ElSayed, Michael Clay, Riarose Contridas, Richard Fox, Glenn Hein, Dan Held, Andrew Horwitz, Stefan Jenkins, Karolina Kalbarczyk, Nandini Krishnamurthy, Mona Mirsiaghi, Katherine Noon, Mike Rowe, Tyson Shepherd, Katia Tarasava, Theodore M Tarasow, Drew Thacker, Gladys Villa, Krishna Yerramsetty
{"title":"Optimizing the strain engineering process for industrial-scale production of bio-based molecules.","authors":"Eric Abbate, Jennifer Andrion, Amanda Apel, Matthew Biggs, Julie Chaves, Kristi Cheung, Anthony Ciesla, Alia Clark-ElSayed, Michael Clay, Riarose Contridas, Richard Fox, Glenn Hein, Dan Held, Andrew Horwitz, Stefan Jenkins, Karolina Kalbarczyk, Nandini Krishnamurthy, Mona Mirsiaghi, Katherine Noon, Mike Rowe, Tyson Shepherd, Katia Tarasava, Theodore M Tarasow, Drew Thacker, Gladys Villa, Krishna Yerramsetty","doi":"10.1093/jimb/kuad025","DOIUrl":"10.1093/jimb/kuad025","url":null,"abstract":"<p><p>Biomanufacturing could contribute as much as ${$}$30 trillion to the global economy by 2030. However, the success of the growing bioeconomy depends on our ability to manufacture high-performing strains in a time- and cost-effective manner. The Design-Build-Test-Learn (DBTL) framework has proven to be an effective strain engineering approach. Significant improvements have been made in genome engineering, genotyping, and phenotyping throughput over the last couple of decades that have greatly accelerated the DBTL cycles. However, to achieve a radical reduction in strain development time and cost, we need to look at the strain engineering process through a lens of optimizing the whole cycle, as opposed to simply increasing throughput at each stage. We propose an approach that integrates all 4 stages of the DBTL cycle and takes advantage of the advances in computational design, high-throughput genome engineering, and phenotyping methods, as well as machine learning tools for making predictions about strain scale-up performance. In this perspective, we discuss the challenges of industrial strain engineering, outline the best approaches to overcoming these challenges, and showcase examples of successful strain engineering projects for production of heterologous proteins, amino acids, and small molecules, as well as improving tolerance, fitness, and de-risking the scale-up of industrial strains.</p>","PeriodicalId":16092,"journal":{"name":"Journal of Industrial Microbiology & Biotechnology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10548853/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10128135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chris Richter, Eva Grafahrend-Belau, Jörg Ziegler, Manish L Raorane, Björn H Junker
{"title":"Improved 13C metabolic flux analysis in Escherichia coli metabolism: application of a high-resolution MS (GC-EI-QTOF) for comprehensive assessment of MS/MS fragments.","authors":"Chris Richter, Eva Grafahrend-Belau, Jörg Ziegler, Manish L Raorane, Björn H Junker","doi":"10.1093/jimb/kuad039","DOIUrl":"10.1093/jimb/kuad039","url":null,"abstract":"<p><p>Gas chromatography-tandem mass spectrometry with electron ionization (GC-EI-MS/MS) provides rich information on stable-isotope labeling for 13C-metabolic flux analysis (13C-MFA). To pave the way for the routine application of tandem MS data for metabolic flux quantification, we aimed to compile a comprehensive library of GC-EI-MS/MS fragments of tert-butyldimethylsilyl (TBDMS) derivatized proteinogenic amino acids. First, we established an analytical workflow that combines high-resolution gas chromatography-quadrupole time-of-flight mass spectrometry and fully 13C-labeled biomass to identify and structurally elucidate tandem MS amino acid fragments. Application of the high-mass accuracy MS procedure resulted into the identification of 129 validated precursor-product ion pairs of 13 amino acids with 30 fragments being accepted for 13C-MFA. The practical benefit of the novel tandem MS data was demonstrated by a proof-of-concept study, which confirmed the importance of the compiled library for high-resolution 13C-MFA.</p><p><strong>One sentence summary: </strong>An analytical workflow that combines high-resolution mass spectrometry (MS) and fully 13C-labeled biomass to identify and structurally elucidate tandem MS amino acid fragments, which provide positional information and therefore offering significant advantages over traditional MS to improve 13C-metabolic flux analysis.</p>","PeriodicalId":16092,"journal":{"name":"Journal of Industrial Microbiology & Biotechnology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10716738/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92154743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}