AIMS MicrobiologyPub Date : 2024-02-20eCollection Date: 2024-01-01DOI: 10.3934/microbiol.2024008
Rana H Abo-Hammam, Mohammed Salah, Sarah Shabayek, Amro Hanora, Samira Zakeer, Randa H Khattab
{"title":"Metagenomic analysis of fecal samples in colorectal cancer Egyptians patients post colectomy: A pilot study.","authors":"Rana H Abo-Hammam, Mohammed Salah, Sarah Shabayek, Amro Hanora, Samira Zakeer, Randa H Khattab","doi":"10.3934/microbiol.2024008","DOIUrl":"10.3934/microbiol.2024008","url":null,"abstract":"<p><p>One of the most prevalent malignancies that significantly affects world health is colorectal cancer (CRC). While genetics are involved in a portion of CRC patients, most cases are sporadic. The microbiome composition could be a new source of tumor initiation and progression. This research was conducted to investigate the microbiota composition of CRC patients post colectomy at taxonomic and functional levels. Using a next-generation sequencing approach, using an Illumina Novaseq 6000, the fecal samples of 13 patients were analyzed and the obtained data was subjected to a bioinformatics analysis. The bacterial abundance and uniqueness varied in CRC patients alongside differences in bacterial counts between patients. <i>Bacteroides fragilis</i>, <i>Bacteroides vulgatus</i>, <i>Escherichia coli</i>, and <i>Fusobacterium nucleatum</i> were among the pro-cancerous microorganisms found. Concurrently, bacteria linked to CRC progression were detected that have been previously linked to metastasis and recurrence. At the same time, probiotic bacteria such as <i>Bifidobacterium dentium</i>, <i>Bifidobacterium bifidum</i>, and <i>Akkermansia muciniphila</i> increased in abundance after colectomies. Additionally, numerous pathways were deferentially enriched in CRC, which emerged from functional pathways based on bacterial shotgun data. CRC-specific microbiome signatures include an altered bacterial composition. Our research showed that microbial biomarkers could be more usefully employed to explore the link between gut microbiota and CRC using metagenomic techniques in the diagnosis, prognosis, and remission of CRC, thereby opening new avenues for CRC treatment.</p>","PeriodicalId":46108,"journal":{"name":"AIMS Microbiology","volume":"10 1","pages":"148-160"},"PeriodicalIF":4.8,"publicationDate":"2024-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10955169/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140207882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AIMS MicrobiologyPub Date : 2024-02-06eCollection Date: 2024-01-01DOI: 10.3934/microbiol.2024007
Fatemeh Aghighi, Mahmoud Salami
{"title":"What we need to know about the germ-free animal models.","authors":"Fatemeh Aghighi, Mahmoud Salami","doi":"10.3934/microbiol.2024007","DOIUrl":"10.3934/microbiol.2024007","url":null,"abstract":"<p><p>The gut microbiota (GM), as a forgotten organ, refers to the microbial community that resides in the gastrointestinal tract and plays a critical role in a variety of physiological activities in different body organs. The GM affects its targets through neurological, metabolic, immune, and endocrine pathways. The GM is a dynamic system for which exogenous and endogenous factors have negative or positive effects on its density and composition. Since the mid-twentieth century, laboratory animals are known as the major tools for preclinical research; however, each model has its own limitations. So far, two main models have been used to explore the effects of the GM under normal and abnormal conditions: the isolated germ-free and antibiotic-treated models. Both methods have strengths and weaknesses. In many fields of host-microbe interactions, research on these animal models are known as appropriate experimental subjects that enable investigators to directly assess the role of the microbiota on all features of physiology. These animal models present biological model systems to either study outcomes of the absence of microbes, or to verify the effects of colonization with specific and known microbial species. This paper reviews these current approaches and gives advantages and disadvantages of both models.</p>","PeriodicalId":46108,"journal":{"name":"AIMS Microbiology","volume":"10 1","pages":"107-147"},"PeriodicalIF":4.8,"publicationDate":"2024-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10955174/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140207884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Extracellular enzymes producing yeasts study: cost-effective production of α-amylase by a newly isolated thermophilic yeast <i>Geotrichum candidum</i> PO27.","authors":"Ibtissem Chaib, Scheherazed Dakhmouche-Djekrif, Leila Bennamoun, Tahar Nouadri","doi":"10.3934/microbiol.2024006","DOIUrl":"10.3934/microbiol.2024006","url":null,"abstract":"<p><p>Enzymes are biocatalysts mainly used for their industrial potential in various applications. The present study aims to understand the enzyme production for biotechnological interest from a local yeast strain. From 100 isolates obtained from various biotopes, 78 strains were selected for their enzymatic heritage. Screening of α-amylase, lipase/esterase, and cellulase activities by rapid plate detection methods was carried out and the PO27 yeast was selected for its high capacity to produce α-amylase. In addition, this yeast strain exhibited good lipolytic and esterolytic activities, as well as low cellulase activity. A sequence analysis of the D1/D2 region of the 26S ribosomal RNA (26S rRNA) and a study of morphological characteristics identified the PO27 strain as <i>Geotrichum candidum</i>. The production of α-amylase has been studied in solid medium fermentation using various natural substrates without any supplementation such as olive pomace, potato peels, leftover bread, and mastic cake. <i>G. candidum</i> PO27 showed an improved production of α-amylase with olive pomace, thus reaching approximately 180.71 U/g. To evaluate the ability of this isolate to produce α-amylase in submerged fermentation, multiple concentrations of olive pomace substrate were tested. The best activity of submerged fermentation was statistically compared to the solid-state fermentation result in order to select the appropriate fermentation type. A high significant difference was found to rank the 6% olive pomace medium as the best substrate concentration with 34.395 U/mL of α-amylase activity. This work showed that the new isolate <i>Geotrichum candidum</i> PO27 has a better potential to produce α-amylase at a low cost in solid-state fermentation compared to submerged fermentation. Optimization conditions for PO27 α-amylase production through solid-state fermentation were achieved using a one factor at a time (OFAT) approach. The findings revealed that a high temperature (60 °C), an acidic pH, malt extract, and soluble starch were the highly significant medium components for enhancing α-amylase production. The use of olive pomace waste by <i>Geotrichum candidum</i> PO27 is expected to be effective in producing an industrially useful α-amylase.</p>","PeriodicalId":46108,"journal":{"name":"AIMS Microbiology","volume":"10 1","pages":"83-106"},"PeriodicalIF":4.8,"publicationDate":"2024-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10955176/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140207880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Diversity and antimicrobial activity of the tropical ant-derived actinomycetes isolated from Thailand.","authors":"Tuangrat Tunvongvinis, Weeyawat Jaitrong, Yudthana Samung, Somboon Tanasupawat, Wongsakorn Phongsopitanun","doi":"10.3934/microbiol.2024005","DOIUrl":"10.3934/microbiol.2024005","url":null,"abstract":"<p><p>Antibiotic resistance is one of the most important global healthcare challenges and is responsible for the mortality of millions of people worldwide every year. It is a crisis attributed to misuse of antibiotics and a lack of new drug development. Actinomycetes constitute a group of Gram-positive bacteria known for their distinctive high guanine-cytosine (G+C) content in their genomic DNA. These microorganisms are widely recognized for their capability to generate a wide range of secondary metabolites with diverse biological activities. These versatile microorganisms are ubiquitous in diverse ecosystems, including soil, freshwater, marine sediments, and within the bodies of insects. A recent study has demonstrated that social insects, such as ants, host a diverse array of these bacteria. In this study, we involved the isolation and characterization of a total of 72 actinomycete strains obtained from 18 distinct ant species collected from various regions across Thailand. Utilizing 16S rRNA gene analysis, these isolated actinomycetes were classified into four distinct genera: <i>Amycolatopsis</i> (2 isolates), <i>Micromonospora</i> (1 isolate), <i>Nocardia</i> (8 isolates), and <i>Streptomyces</i> (61 isolates). Among the <i>Streptomyces</i> strains, 23 isolates exhibited antimicrobial activity against a panel of Gram-positive bacteria, including <i>Bacillus subtilis</i> ATCC 6633, <i>Staphylococcus epidermidis</i> ATCC 12228, <i>Staphylococcus aureus</i> ATCC 25923, <i>Kocuria rhizophila</i> ATCC 9341, and Methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) DMST 20646. Additionally, two isolates displayed antifungal activity against <i>Candida albicans</i> TISTR 5554. Based on 16S rRNA gene sequence similarity studies, these two isolates, ODS25 and ODS28, were demonstrated to be closely related to <i>Streptomyces lusitanus</i> NBRC 13464<sup>T</sup> (98.07%) and <i>Streptomyces haliclonae</i> DSM 41970<sup>T</sup> (97.28%), respectively. The level of 16S rRNA gene sequence similarity below 98.65% cutoff indicates its potential as a novel actinomycete species. These findings underscore the potential of actinomycetes sourced from ants as a valuable reservoir of novel antimicrobials.</p>","PeriodicalId":46108,"journal":{"name":"AIMS Microbiology","volume":"10 1","pages":"68-82"},"PeriodicalIF":4.8,"publicationDate":"2024-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10955170/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140207879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AIMS MicrobiologyPub Date : 2024-01-17eCollection Date: 2024-01-01DOI: 10.3934/microbiol.2024003
Ana M Castañeda-Meléndrez, José A Magaña-Lizárraga, Marcela Martínez-Valenzuela, Aldo F Clemente-Soto, Patricia C García-Cervantes, Francisco Delgado-Vargas, Rodolfo Bernal-Reynaga
{"title":"Genomic characterization of a multidrug-resistant uropathogenic <i>Escherichia coli</i> and evaluation of <i>Echeveria</i> plant extracts as antibacterials.","authors":"Ana M Castañeda-Meléndrez, José A Magaña-Lizárraga, Marcela Martínez-Valenzuela, Aldo F Clemente-Soto, Patricia C García-Cervantes, Francisco Delgado-Vargas, Rodolfo Bernal-Reynaga","doi":"10.3934/microbiol.2024003","DOIUrl":"10.3934/microbiol.2024003","url":null,"abstract":"<p><p>Uropathogenic <i>Escherichia coli</i> (UPEC) is the most common bacterial agent associated with urinary tract infections, threatening public health systems with elevated medical costs and high morbidity rates. The successful establishment of the infection is associated with virulence factors encoded in its genome, in addition to antibacterial resistance genes, which could limit the treatment and resolution of the infection. In this sense, plant extracts from the genus <i>Echeveria</i> have traditionally been used to treat diverse infectious diseases. However, little is known about the effects of these extracts on bacteria and their potential mechanisms of action. This study aims to sequence a multidrug-resistant UPEC isolate (UTI-U7) and assess the multilocus sequence typing (MLST), virulence factors, antimicrobial resistance profile, genes, serotype, and plasmid content. Antimicrobial susceptibility profiling was performed using the Kirby-Bauer disk diffusion. The antibacterial and anti-adherent effects of the methanol extracts (ME) of <i>Echeveria</i> (<i>E. craigiana</i>, <i>E. kimnachii</i>, and <i>E. subrigida</i>) against UTI-U7 were determined. The isolate was characterized as an O25:H4-B2-ST2279-CH40 subclone and had resistant determinants to aminoglycosides, β-lactams, fluoroquinolones/quinolones, amphenicols, and tetracyclines, which matched with the antimicrobial resistance profile. The virulence genes identified encode adherence factors, iron uptake, protectins/serum resistance, and toxins. Identified plasmids belonged to the IncF group (IncFIA, IncFIB, and IncFII), alongside several prophage-like elements. After an extensive genome analysis that confirmed the pathogenic status of UTI-U7 isolate, <i>Echeveria</i> extracts were tested to determine their antibacterial effects; as an extract, <i>E. subrigida</i> (MIC, 5 mg/mL) displayed the best inhibitory effect. However, the adherence between UTI-U7 and HeLa cells was unaffected by the ME of the <i>E. subrigida</i> extract.</p>","PeriodicalId":46108,"journal":{"name":"AIMS Microbiology","volume":"10 1","pages":"41-61"},"PeriodicalIF":4.8,"publicationDate":"2024-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10955171/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140207881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AIMS MicrobiologyPub Date : 2024-01-16eCollection Date: 2024-01-01DOI: 10.3934/microbiol.2024002
Helene Nalini Chinivasagam, Wiyada Estella, Damien Finn, David G Mayer, Hugh Rodrigues, Ibrahim Diallo
{"title":"Broiler farming practices using new or re-used bedding, inclusive of free-range, have no impact on <i>Campylobacter</i> levels, species diversity, <i>Campylobacter</i> community profiles and <i>Campylobacter</i> bacteriophages.","authors":"Helene Nalini Chinivasagam, Wiyada Estella, Damien Finn, David G Mayer, Hugh Rodrigues, Ibrahim Diallo","doi":"10.3934/microbiol.2024002","DOIUrl":"10.3934/microbiol.2024002","url":null,"abstract":"<p><p>A multi-stage option to address food-safety can be produced by a clearer understanding of <i>Campylobacter</i>'s persistence through the broiler production chain, its environmental niche and its interaction with bacteriophages. This study addressed <i>Campylobacter</i> levels, species, genotype, bacteriophage composition/ levels in caeca, litter, soil and carcasses across commercial broiler farming practices to inform on-farm management, including interventions. Broilers were sequentially collected as per company slaughter schedules over two-years from 17 farms, which represented four commercially adopted farming practices, prior to the final bird removal (days 39-53). The practices were conventional full clean-out, conventional litter re-use, free-range-full cleanout and free-range-litter re-use. Caeca, litter and soil collected on-farm, and representative carcases collected at the processing plant, were tested for <i>Campylobacter</i> levels, species dominance and <i>Campylobacter</i> bacteriophages. General community profiling via denaturing gradient gel electrophoresis of the <i>flaA</i> gene was used to establish the population relationships between various farming practices on representative <i>Campylobacter</i> isolates. The farming practice choices did not influence the high caeca <i>Campylobacter</i> levels (log 7.5 to log 8.5 CFU/g), the carcass levels (log 2.5 to log 3.2 CFU/carcass), the <i>C. jejuni</i>/<i>C. coli</i> dominance and the on-farm bacteriophage presence/levels. A principal coordinate analysis of the <i>flaA</i> distribution for farm and litter practices showed strong separation but no obvious farming practice related grouping of <i>Campylobacter</i>. Bacteriophages originated from select farms, were not practice-dependent, and were detected in the environment (litter) only if present in the birds (caeca). This multifaceted study showed no influence of farming practices on on-farm <i>Campylobacter</i> dynamics. The significance of this study means that a unified on-farm risk-management could be adopted irrespective of commercial practice choices to collectively address caeca <i>Campylobacter</i> levels, as well as the potential to include <i>Campylobacter</i> bacteriophage biocontrol. The impact of this study means that there are no constraints in re-using bedding or adopting free-range farming, thus contributing to environmentally sustainable (re-use) and emerging (free-range) broiler farming choices.</p>","PeriodicalId":46108,"journal":{"name":"AIMS Microbiology","volume":"10 1","pages":"12-40"},"PeriodicalIF":4.8,"publicationDate":"2024-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10955168/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140207878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Seroprevalence of brucellosis among animal handlers in West Bengal, India: an occupational health study.","authors":"Dolanchampa Modak, Silpak Biswas, Agnibho Mondal, Malabika Biswas, Maria Teresa Mascellino, Banya Chakraborty, Simmi Tiwari, Ajit Dadaji Shewale, Tushar Nale, Rupali Dey","doi":"10.3934/microbiol.2024001","DOIUrl":"10.3934/microbiol.2024001","url":null,"abstract":"<p><p>Brucellosis is a highly contagious zoonotic disease and a major human health problem worldwide. Due to its ways of transmission, direct or indirect contact with infected animals or their contaminated biological products, the disease exhibits strong occupational association with animal handlers comprising a significant population at risk. This study was undertaken to estimate the seroprevalence of brucellosis in animal handlers and to understand the epidemiological and serological aspects of the same. The animal handlers from the state of West Bengal, India were included in this study. It was a prospective and observational cohort study from November 2021 to March 2022. A total of 669 sera samples were collected from animal handlers and tested using various serological tests for <i>Brucella</i> antibodies. All serum samples were tested using the Rose Bengal plate test (RBPT), standard tube agglutination test (STAT), and enzyme-linked immunosorbent assay (ELISA). 106 (15.8%) patients were diagnosed with brucellosis among the total number of patients tested. Most of the patients affected with brucellosis belonged to the age group 51-60 years (23.5%). The seropositivity rate in male animal handlers was higher than female animal handlers in this study. More studies are needed to understand the occupational association of this disease. Awareness programs, safe livestock practices, and prevention of the disease by timely diagnosis must be implemented in order to control human brucellosis.</p>","PeriodicalId":46108,"journal":{"name":"AIMS Microbiology","volume":"10 1","pages":"1-11"},"PeriodicalIF":4.8,"publicationDate":"2024-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10955173/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140207883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AIMS MicrobiologyPub Date : 2023-12-18eCollection Date: 2023-01-01DOI: 10.3934/microbiol.2023040
Zeling Xu, Shuzhen Chen, Weiyan Wu, Yongqi Wen, Huiluo Cao
{"title":"Type I CRISPR-Cas-mediated microbial gene editing and regulation.","authors":"Zeling Xu, Shuzhen Chen, Weiyan Wu, Yongqi Wen, Huiluo Cao","doi":"10.3934/microbiol.2023040","DOIUrl":"10.3934/microbiol.2023040","url":null,"abstract":"<p><p>There are six major types of CRISPR-Cas systems that provide adaptive immunity in bacteria and archaea against invasive genetic elements. The discovery of CRISPR-Cas systems has revolutionized the field of genetics in many organisms. In the past few years, exploitations of the most abundant class 1 type I CRISPR-Cas systems have revealed their great potential and distinct advantages to achieve gene editing and regulation in diverse microorganisms in spite of their complicated structures. The widespread and diversified type I CRISPR-Cas systems are becoming increasingly attractive for the development of new biotechnological tools, especially in genetically recalcitrant microbial strains. In this review article, we comprehensively summarize recent advancements in microbial gene editing and regulation by utilizing type I CRISPR-Cas systems. Importantly, to expand the microbial host range of type I CRISPR-Cas-based applications, these structurally complicated systems have been improved as transferable gene-editing tools with efficient delivery methods for stable expression of CRISPR-Cas elements, as well as convenient gene-regulation tools with the prevention of DNA cleavage by obviating deletion or mutation of the Cas3 nuclease. We envision that type I CRISPR-Cas systems will largely expand the biotechnological toolbox for microbes with medical, environmental and industrial importance.</p>","PeriodicalId":46108,"journal":{"name":"AIMS Microbiology","volume":"9 4","pages":"780-800"},"PeriodicalIF":2.7,"publicationDate":"2023-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10758571/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139088964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AIMS MicrobiologyPub Date : 2023-12-18eCollection Date: 2023-01-01DOI: 10.3934/microbiol.2023039
Chengcang C Wu, Andrea A Stierle, Donald B Stierle, Hongyu Chen, Michael Swyers, Timothy Decker, Emili Borkowski, Peter Korajczyk, Rosa Ye, Niel Mondava
{"title":"Activation of cryptic biosynthetic gene clusters by fungal artificial chromosomes to produce novel secondary metabolites.","authors":"Chengcang C Wu, Andrea A Stierle, Donald B Stierle, Hongyu Chen, Michael Swyers, Timothy Decker, Emili Borkowski, Peter Korajczyk, Rosa Ye, Niel Mondava","doi":"10.3934/microbiol.2023039","DOIUrl":"10.3934/microbiol.2023039","url":null,"abstract":"<p><p>In 2017, we reported the discovery of Berkeleylactone A (BPLA), a novel, potent antibiotic produced exclusively in co-culture by two extremophilic fungi, <i>Penicillium fuscum</i> and <i>P. camembertii/clavigerum</i>, which were isolated from the Berkeley Pit, an acid mine waste lake, in Butte, Montana. Neither fungus synthesized BPLA when grown in axenic culture. Recent studies suggest that secondary metabolites (SMs) are often synthesized by enzymes encoded by co-localized genes that form \"biosynthetic gene clusters\" (BGCs), which might remain <i>silent</i> (inactive) under various fermentation conditions. Fungi may also harbor cryptic BGCs that are not associated with previously characterized molecules. We turned to the tools of Fungal Artificial Chromosomes (FAC)-Next-Gen-Sequencing (NGS) to understand how co-culture activated cryptic biosynthesis of BPLA and several related berkeleylactones and to further investigate the true biosynthetic potential of these two fungi. FAC-NGS enables the capture of BGCs as individual FACs for heterologous expression in a modified strain of <i>Aspergillus nidulans</i> (heterologous host, FAC-<i>An</i>HH). With this methodology, we created ten BGC-FACs that yielded fourteen different SMs, including strobilurin, which was previously isolated exclusively from basidiomycetes. Eleven of these compounds were not detected in the extracts of the FAC-<i>An</i>HH. Of this discrete set, only the novel compound citreohybriddional had been isolated from either <i>Penicillium</i> sp. before and only at very low yield. We propose that through heterologous expression, FACs activated these silent BGCs, resulting in the synthesis of new natural products (NPs) with yields as high as 50%-60% of the crude organic extracts.</p>","PeriodicalId":46108,"journal":{"name":"AIMS Microbiology","volume":"9 4","pages":"757-779"},"PeriodicalIF":4.8,"publicationDate":"2023-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10758572/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139088931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}