Article
Biotechnology & Applied Microbiology
Susann Schulz, Christoph Schall, Thilo Stehle, Christian Breitmeyer, Sergii Krysenko, Agnieszka Mitulski, Wolfgang Wohlleben
Summary: Engineering of the lysine biosynthetic pathway and FK506 biosynthesis pathway, as well as overexpression of feedback deregulated enzymes, led to significant increases in FK506 yield. The indispensability of lysine cyclodeaminase FkbL for FK506 production was confirmed by construction of a ΔfkbL mutant. Restoration of FK506 production was achieved through chemical and genetic complementation after disrupting the fkbL gene. Through rational genetic modification based on structural analysis, a significant increase in FK506 production was achieved.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Hai-Tao Chen, Xiao-Ying Zhang, Qing-Bin Wu, Qing-Wei Zhao, Xin-Ai Chen, Yong-Quan Li
Summary: The effect of isoleucine on FK506 biosynthesis was studied, and the producing strain was modified to improve the production of FK506. Metabolomics analysis revealed that the shikimate pathway, methylmalonyl-CoA, and pyruvate might be the rate-limiting factors in FK506 biosynthesis. Overexpression of the gene PCCB1 and addition of isoleucine and valine increased the yield of FK506 by 56.6%.
JOURNAL OF APPLIED MICROBIOLOGY
(2023)
Article
Biotechnology & Applied Microbiology
Qing-Bin Wu, Xiao-Ying Zhang, Xin-Ai Chen, Yong-Quan Li
Summary: By deleting competitive pathways, refactoring the FK506 biosynthetic gene cluster, and adding nutrients, a strategy for hyper-production of FK506 was successfully developed, leading to the construction of a hyper-production strain L19-9. This strategy can be generally applicable to other Streptomyces for improving FK506 production and streamlining hyper-production of other valuable secondary metabolites.
MICROBIAL CELL FACTORIES
(2021)
Article
Chemistry, Multidisciplinary
Kathrin Buntin, Peter Mrak, Petra Pivk Lukancic, Severine Wollbrett, Tjasa Drcar, Philipp Krastel, Christian Thibaut, Michael Salcius, Xiaolin Gao, Shaowen Wang, Eric Weber, Eva Koplan, Hugo Regenass
Summary: For a potential application of FK506 in the treatment of acute kidney failure, it is necessary to only have the binding capability of the compound to FKBP12, while the immunosuppressive activity via calcineurin binding is considered to be a risk. The presence of methoxy groups at C13 and C15 is believed to significantly affect the immunosuppressive activity of the molecule. Therefore, FK506 analogs with different functionalities at C13 and C15 were generated to study their bioactivity in relation to FKBP12 binding, BMP potentiation, and calcineurin sparing. Among the tested analogs, 15-desmethoxy FK506 was found to have superior properties as it did not inhibit calcineurin but retained high potency towards FKBP12 binding and BMP potentiation.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Biochemistry & Molecular Biology
Xiaoying Zhang, Qingbin Wu, Xiaoyuan Zhang, Zhongyuan Lv, Xiaoting Mo, Yongquan Li, Xin-ai Chen
Summary: FK506, an immunosuppressive agent, production was enhanced through strategies including overexpression of regulatory genes and optimization of growth medium, reaching a maximum titer of 756 mg/L in a 5 L fermenter. This study provides insights for potential industrial applications of FK506.
PROCESS BIOCHEMISTRY
(2021)
Article
Biochemical Research Methods
Huang-jian Yang, Zhu-lan Zhang, Ling-bin Yan, Zhou-qin Chen, Xian ju Lin, Xian Cheng, Jing-ming Zhou, De -sen Wang, Yun-yang Lian
Summary: In this study, a modified nanoscale polymeric adsorbent, Ag +-exchanged resin, was prepared and studied for the preprative separation and purification of tacrolimus, achieving high purity and recovery.
JOURNAL OF CHROMATOGRAPHY A
(2022)
Article
Biotechnology & Applied Microbiology
Qing-Bin Wu, Xin-Ai Chen, Zhong-Yuan Lv, Xiao-Ying Zhang, Yu Liu, Yong-Quan Li
Summary: Genome sequencing has uncovered hidden biosynthetic gene clusters in Streptomyces, leading to the discovery of a novel anthracycline with superior antitumor activities than current chemotherapy drugs. This strategy of gene cluster activation and screening is applicable to other Streptomyces species, offering potential drug leads from natural products.
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
(2021)
Article
Agricultural Engineering
Syeda Warisul Fatima, Sunil K. Khare
Summary: The study describes the regulatory mechanism of microbial Transglutaminase (MTGase) biosynthesis from Streptomyces mobaraensis and the effect of key regulators on maximizing production. Through the optimization by combinational supplementation of key modulators, there was a significant increase in productivity and activity of MTGase.
BIORESOURCE TECHNOLOGY
(2021)
Article
Biotechnology & Applied Microbiology
Ruida Wang, Jiaqi Zhao, Lei Chen, Jiang Ye, Haizhen Wu, Huizhan Zhang
Summary: In this study, it was identified that LcbR1 functions as a repressor for lincomycin biosynthesis in Streptomyces lincolnensis. LcbR1 suppresses the transcription of lcbR1 itself and SLINC_1596, resulting in an increase in lincomycin production. The expression of lcbR1 may be regulated by GlnR, SLCG_Lrp, and SLCG_2919.
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
(2023)
Article
Plant Sciences
Hanmei Liu, Yongbin Wang, Lijun Liu, Bin Wei, Xieqin Wang, Qianlin Xiao, Yangping Li, Babatope Samuel Ajayo, Yubi Huang
Summary: This study identified 202 bHLH encoding genes in the maize genome, and found that the ZmICE1 gene is expressed in maize filling endosperm and is co-expressed with 14 starch biosynthesis genes. Comparative analyses revealed that the gene structures and protein domains of the ICE subfamily were conserved between monocots and dicots. Functional experiments showed that ZmICE1 has transcriptional activation activity and is localized in the nucleus. It was also found that ZmICE1 can directly bind to the promoters of ZmSSIIa and ZmGBSSI, positively regulating the expression of ZmSSIIa and inhibiting the expression of ZmGBSSI.
FRONTIERS IN PLANT SCIENCE
(2022)
Article
Biotechnology & Applied Microbiology
Susann Schulz, Havard Sletta, Kristin Flogstad Degnes, Sergii Krysenko, Alicia Williams, Silje Malene Olsen, Kai Vernstad, Agnieszka Mitulski, Wolfgang Wohlleben
Summary: FK-506 is a potent immunosuppressive macrocyclic polyketide produced by Streptomyces tsukubaensis, but its biotechnological production is limited due to low levels synthesized by the wild-type strain. This study investigated the global regulatory aspects of FK-506 biosynthesis, particularly focusing on the role of the Crp regulator. Crp overexpression led to a two-fold increase in FK-506 production, which was successfully transferred to industrial scale using fermentors.
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
(2023)
Article
Biotechnology & Applied Microbiology
Ruida Wang, Yuan Cao, Fanjing Kong, Bingbing Hou, Jiaqi Zhao, Yajing Kang, Jiang Ye, Haizhen Wu, Huizhan Zhang
Summary: The gene ramR(sl) plays a role in the regulation of morphological development and lincomycin biosynthesis in Streptomyces lincolnensis. Deletion of ramR(sl) led to increased lincomycin production and altered expression of known biosynthesis regulators. These findings suggest that RamR may be a potential target for improving antibiotic production in other Streptomyces strains.
JOURNAL OF APPLIED MICROBIOLOGY
(2022)
Article
Infectious Diseases
Claudia M. Vicente, Tamara D. Payero, Antonio Rodriguez-Garcia, Eva G. Barreales, Antonio de Pedro, Fernando Santos-Beneit, Jesus F. Aparicio
Summary: PteF gene has been found to regulate filipin biosynthesis in the Streptomyces strain, causing changes in the expression of various metabolic processes and secondary metabolite genes. Despite being considered an activator, most of the affected genes showed overexpression, indicating a negative modulation. These findings have important implications for understanding the regulatory mechanisms of antibiotic biosynthesis in Streptomyces.
Article
Biotechnology & Applied Microbiology
Qian Wang, Xiaorui Lu, Haixin Yang, Hao Yan, Ying Wen
Summary: SoxR plays a pleiotropic role in regulating antibiotic production, morphological development, primary metabolism, and stress response in Streptomyces avermitilis. It directly activates specific genes involved in avermectin production, development, biosynthesis, metabolism, and transport, leading to enhanced antibiotic overproduction. Additionally, SoxR promotes resistance to thiol-oxidative stress by activating target genes in Streptomyces species.
MICROBIAL BIOTECHNOLOGY
(2022)
Article
Infectious Diseases
Qiong Chen, Jianya Zhu, Xingwang Li, Ying Wen
Summary: The GntR family transcriptional regulator DasR was found to regulate the production of daptomycin and reddish pigment, as well as morphological development in Streptomyces roseosporus. DasR repressed the dpt structural genes and adpA gene to inhibit daptomycin production, while AdpA targeted the dpt structural genes and dptR2 gene to promote daptomycin production.
Article
Biotechnology & Applied Microbiology
Miriam Martinez-Castro, Carlos Barreiro, Juan F. Martin
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
(2018)
Article
Biochemical Research Methods
Mohammad-Saeid Jami, Juan-Francisco Martin, Carlos Barreiro, Rebeca Dominguez-Santos, Maria-Femanda Vasco-Cardenas, Maria Pascual, Carlos Garcia-Estrada
JOURNAL OF PROTEOMICS
(2018)
Review
Biotechnology & Applied Microbiology
Carlos Barreiro, Miriam Martinez-Castro
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
(2019)
Article
Biochemical Research Methods
Carlos Barreiro, Carlos Garcia-Estrada
JOURNAL OF PROTEOMICS
(2019)
Article
Neurosciences
Sedigheh Momenzadeh, Saeed Zamani, Fariba Dehghan, Carlos Barreiro, Mohammad-Saeid Jami
Summary: The hormone irisin is proposed as an effector of exercise on the nervous system, with potential to improve nerve function and maintain cell homeostasis. Studies showed that irisin administration can regulate nerve metabolism, enhance axonal transport, and induce neurotrophic support on the sciatic nerve, suggesting its therapeutic potential for peripheral neuropathies and nerve injuries.
EUROPEAN JOURNAL OF NEUROSCIENCE
(2021)
Review
Food Science & Technology
Laura Ramos, Alicia Alonso-Hernando, Miriam Martinez-Castro, Jose Alejandro Moran-Perez, Patricia Cabrero-Lobato, Ana Pascual-Mate, Eduardo Tellez-Jimenez, Jorge R. Mujico
Summary: Recent studies suggest that sourdough fermentation may be beneficial for the development of new gluten-free products to improve their technological and nutritional properties. Additives like hydrocolloids, proteins, enzymes, and emulsifiers are commonly used to enhance the technological performance of gluten-free products. Sourdough biotechnology, mimicking gluten molecules, shows great potential in the field of gluten-free products.
Article
Microbiology
Rebeca Dominguez-Santos, Katarina Kosalkova, Isabel-Clara Sanchez-Orejas, Carlos Barreiro, Yolanda Perez-Pertejo, Rosa M. Reguera, Rafael Balana-Fouce, Carlos Garcia-Estrada
Summary: This article describes the use of the filamentous fungus Penicillium chrysogenum in the industrial production of penicillin and highlights the role of AdoMet synthetase in both primary and secondary metabolism in this process.
Article
Microbiology
Oscar Velasco-Rodriguez, Mariana Fil, Tonje M. B. Heggeset, Kristin F. Degnes, David Becerro-Recio, Katarina Kolsakova, Tone Haugen, Malene Jonsson, Macarena Toral-Martinez, Carlos Garcia-Estrada, Alberto Sola-Landa, Kjell D. Josefsen, Havard Sletta, Carlos Barreiro
Summary: This study found that bacterial diversity in decaying wood was higher than fungal heterogeneity, with 194 different cultivable bacterial isolates mainly belonging to Bacillaceae, Streptomycetaceae, Paenibacillaceae, and Microbacteriaceae, and 343 fungal strains mainly belonging to Aspergillaceae, Hypocreaceae, and Coniochaetaceae. The results also suggest that decaying wood is an ecologically rich niche and a promising source of biotechnologically interesting microorganisms.
Article
Biotechnology & Applied Microbiology
Laura Garcia-Calvo, Raquel Rodriguez-Castro, Ricardo Ullan, Silvia M. Albillos, Marta Fernandez-Aguado, Claudia M. Vicente, Kristin F. Degnes, Havard Sletta, Carlos Barreiro
Summary: This study identified a potential lignocellulolytic enzyme producer, Penicillium rubens, which overexpressed two genes (PrFaeA and PrFaeB) with feruloyl esterase (FAE) activity. Enzyme extracts from PrFaeB-enriched cultures showed optimal FAE activity at pH 5.0 and 50-55 degrees C, as confirmed by proteome analysis and mass spectrometry. The study also analyzed other lignocellulolytic activities, untargeted metabolites, and scaled up FAE production in stirred tank reactors. These findings highlight the potential of P. rubens as a promising lignocellulolytic enzyme producer.
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
(2023)
Review
Microbiology
Katarina Kosalkova, Carlos Barreiro, Isabel-Clara Sanchez-Orejas, Laura Cueto, Carlos Garcia-Estrada
Summary: Cannabinoids are bioactive compounds that can modulate various physiological processes. They have shown potential for medical/therapeutic effects and can be produced through heterologous biosynthetic platforms developed by genetic engineering in fungi. This approach offers advantages over extraction or chemical synthesis.
Article
Biochemistry & Molecular Biology
Ana Ibanez, Carlos Barreiro, Alba Diez-Galan, Rebeca Cobos, Carla Calvo-Pena, Juan Jose R. Coque
Summary: This study develops a taxonomic assignment method for Acidithiobacillus thiooxidans based on the sequencing of the 16S-5S rRNA cluster and a qPCR-based technology for accurate growth determination. The study also investigates the response of Acidithiobacillus thiooxidans to acid stress through RT-PCR and MALDI-TOF analysis. The findings suggest that the cell inhibits central and energy metabolism when subjected to pH levels below 1, while enhancing ammonia secretion and fatty acid synthesis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Genetics & Heredity
Ana Ibanez, Sonia Garrido-Chamorro, Juan J. R. Coque, Carlos Barreiro
Summary: This review summarizes the latest research progress on sulfur metabolic processes in Acidithiobacillus species, which play a crucial role in industrial biomining processes. The challenges and barriers to further study the sulfur metabolism of this peculiar extremophilic genus are also highlighted.
Article
Genetics & Heredity
Luis Getino, Alejandro Chamizo-Ampudia, Jose Luis Martin, Jose Maria Luengo, Carlos Barreiro, Elias R. Olivera
Summary: Pseudomonas putida strain U can utilize putrescine, cadaverine, and their catabolic derivatives as sole carbon sources for growth. The expression of genes involved in the catabolism of these compounds varies depending on the carbon source supplied. These findings provide insights into the differences in polyamine catabolism mechanisms between P. putida strain U and other bacteria, and shed light on the enzymatic systems used by this strain during polyamine metabolism.