Suhui Ye Huang

Scopus Publications

Corneal stromal cells from patients with keratoconus exhibit alterations in the ESCRT-dependent machinery responsible for multivesicular body formation
Noelia Blanco-Agudín, Suhui Ye, Ignacio Alcalde, María Daniela Corte-Torres, David Galarreta, Manuel Caro-Magdaleno, Iván Fernández-Vega, Luis Fernández-Vega Cueto, Jesús Merayo-Lloves, Luis M. Quirós
Experimental Eye Research, 2025
Exosomes in Ocular Health: Recent Insights into Pathology, Diagnostic Applications and Therapeutic Functions
Noelia Blanco-Agudín, Suhui Ye, Sara González-Fernández, Ignacio Alcalde, Jesús Merayo-Lloves, Luis M. Quirós
Biomedicines, 2025
Exosomes are extracellular vesicles ranging from 30 to 150 nm in diameter that contain proteins, nucleic acids and other molecules. Produced by virtually all cell types, they travel throughout the body until they reach their target, where they can trigger a wide variety of effects by transferring the molecular cargo to recipient cells. In the context of ocular physiology, exosomes play a very important role in embryological development, the regulation of homeostasis and the immune system, which is crucial for normal vision. Consequently, in pathological situations, exosomes also undergo modifications in terms of quantity, composition and content, depending on the etiology of the disease. However, the mechanisms by which exosomes contribute to ocular pathology has not yet been studied in depth, and many questions remain unanswered. This review aims to summarize the most recent knowledge on the function of exosomes in the ocular system in healthy individuals and the role they play during pathological processes of a degenerative, infectious, neurodegenerative, vascular and inflammatory nature, such as keratoconus, keratitis, glaucoma, diabetic retinopathy and uveitis. Furthermore, given their unique characteristics, their potential as diagnostic biomarkers or therapeutic agents and their application in clinical ophthalmology are also explored, along with the main limitations that researchers face today in the field.
Identification of a polyphenol O-methyltransferase with broad substrate flexibility in Streptomyces albidoflavus J1074
Álvaro Pérez-Valero, Patricia Magadán-Corpas, Kinga Dulak, Agata Matera, Suhui Ye, Ewa Huszcza, Jarosław Popłoński, Claudio J. Villar, Felipe Lombó
Microbial Cell Factories, 2024
Flavonoids are a large and important group of phytochemicals with a great variety of bioactivities. The addition of methyl groups during biosynthesis of flavonoids and other polyphenols enhances their bioactivities and increases their stability. In a previous study of our research group, we detected a novel flavonoid O-methyltransferase activity in Streptomyces albidoflavus J1074, which led to the heterologous biosynthesis of homohesperetin from hesperetin in feeding cultures. In this study, we identify the O-methyltransferase responsible for the generation of this methylated flavonoid through the construction of a knockout mutant of the gene XNR_0417, which was selected after a blast analysis using the sequence of a caffeic acid 3'-O-methyltransferase from Zea mays against the genome of S. albidoflavus J1074. This mutant strain, S. albidoflavus ∆XNR_0417, was no longer able to produce homohesperetin after hesperetin feeding. Subsequently, we carried out a genetic complementation of the mutant strain in order to confirm that the enzyme encoded by XNR_0417 is responsible for the observed O-methyltransferase activity. This new strain, S. albidoflavus SP43-XNR_0417, was able to produce not only homohesperetin from hesperetin, but also different mono-, di-, tri- and tetra-methylated derivatives on other flavanones, flavones and stilbenes, revealing a broad substrate flexibility. Additionally, in vitro experiments were conducted using the purified enzyme on the substrates previously tested in vivo, demonstrating doubtless the capability of XNR_0417 to generate various methylated derivatives.
Genome Mining for Diazo-Synthesis-Related Genes in Streptomyces sp. CS057 Unveiled the Cryptic Biosynthetic Gene Cluster crx for the Novel 3,4-AHBA-Derived Compound Crexazone 2
Laura Prado-Alonso, Suhui Ye, Ignacio Pérez-Victoria, Ignacio Montero, Pedro Riesco, Francisco Javier Ortiz-López, Jesús Martín, Carlos Olano, Fernando Reyes, Carmen Méndez
Biomolecules, 2024
Natural products play a crucial role in drug development, addressing the escalating microbial resistance to antibiotics and the treatment of emerging diseases. Progress in genome sequencing techniques, coupled with the development of bioinformatics tools and the exploration of uncharted habitats, has highlighted the biosynthetic potential of actinomycetes. By in silico screening for diazo-related gene genomes from twelve Streptomyces strains isolated from Attini leaf-cutting ants, the new crx biosynthetic gene cluster (BGC) was identified in Streptomyces sp. CS057. This cluster, highly conserved in several Streptomyces strains, contains genes related to diazo group formation and genes for the biosynthesis of 3,4-AHBA. By overexpressing the LuxR-like regulatory gene crxR1, we were able to activate the crx cluster, which encodes the biosynthesis of three 3,4-AHBA-derived compounds that we named crexazones (CRXs). The chemical structure of crexazones (CRXs) was determined by LC-DAD-HRMS-based dereplication and NMR spectroscopic analyses and was found to correspond to two known compounds, 3-acetamido-4-hydroxybenzoic acid (CRX1) and the phenoxazinone texazone (CRX3), and a novel 3,4-AHBA-containing compound herein designated as CRX2. Experimental proof linking the crx BGC to their encoded compounds was achieved by generating mutants in selected crx genes.
Antitumor Effect and Gut Microbiota Modulation by Quercetin, Luteolin, and Xanthohumol in a Rat Model for Colorectal Cancer Prevention
Álvaro Pérez-Valero, Patricia Magadán-Corpas, Suhui Ye, Juan Serna-Diestro, Sandra Sordon, Ewa Huszcza, Jarosław Popłoński, Claudio J. Villar, Felipe Lombó
Nutrients, 2024
Colorectal cancer stands as the third most prevalent form of cancer worldwide, with a notable increase in incidence in Western countries, mainly attributable to unhealthy dietary habits and other factors, such as smoking or reduced physical activity. Greater consumption of vegetables and fruits has been associated with a lower incidence of colorectal cancer, which is attributed to their high content of fiber and bioactive compounds, such as flavonoids. In this study, we have tested the flavonoids quercetin, luteolin, and xanthohumol as potential antitumor agents in an animal model of colorectal cancer induced by azoxymethane and dodecyl sodium sulphate. Forty rats were divided into four cohorts: Cohort 1 (control cohort), Cohort 2 (quercetin cohort), Cohort 3 (luteolin cohort), and Cohort 4 (xanthohumol cohort). These flavonoids were administered intraperitoneally to evaluate their antitumor potential as pharmaceutical agents. At the end of the experiment, after euthanasia, different physical parameters and the intestinal microbiota populations were analyzed. Luteolin was effective in significantly reducing the number of tumors compared to the control cohort. Furthermore, the main significant differences at the microbiota level were observed between the control cohort and the cohort treated with luteolin, which experienced a significant reduction in the abundance of genera associated with disease or inflammatory conditions, such as Clostridia UCG-014 or Turicibacter. On the other hand, genera associated with a healthy state, such as Muribaculum, showed a significant increase in the luteolin cohort. These results underline the anti-colorectal cancer potential of luteolin, manifested through a modulation of the intestinal microbiota and a reduction in the number of tumors.
Gut Microbiota and Inflammation Modulation in a Rat Model for Ulcerative Colitis after the Intraperitoneal Administration of Apigenin, Luteolin, and Xanthohumol
Patricia Magadán-Corpas, Álvaro Pérez-Valero, Suhui Ye, Sandra Sordon, Ewa Huszcza, Jarosław Popłoński, Claudio J. Villar, Felipe Lombó
International Journal of Molecular Sciences, 2024
Ulcerative colitis (UC) is a chronic inflammatory disorder affecting the colon, with symptomatology influenced by factors including environmental, genomic, microbial, and immunological interactions. Gut microbiota dysbiosis, characterized by bacterial population alterations, contributes to intestinal homeostasis disruption and aberrant immune system activation, thereby exacerbating the inflammatory state. This study assesses the therapeutic efficacy of intraperitoneal (IP) injected flavonoids (apigenin, luteolin, and xanthohumol) in the reduction of inflammatory parameters and the modulation of the gut microbiota in a murine model of ulcerative colitis. Flavonoids interact with gut microbiota by modulating their composition and serving as substrates for the fermentation into other anti-inflammatory bioactive compounds. Our results demonstrate the effectiveness of luteolin and xanthohumol treatment in enhancing the relative abundance of anti-inflammatory microorganisms, thereby attenuating pro-inflammatory species. Moreover, all three flavonoids exhibit efficacy in the reduction of pro-inflammatory cytokine levels, with luteolin strongly demonstrating utility in alleviating associated physical UC symptoms. This suggests that this molecule is a potential alternative or co-therapy to conventional pharmacological interventions, potentially mitigating their adverse effects. A limited impact on microbiota is observed with apigenin, and this is attributed to its solubility constraints via the chosen administration route, resulting in its accumulation in the mesentery.
Optimization of flavanonols heterologous biosynthesis in Streptomyces albidoflavus, and generation of auronols
Patricia Magadán-Corpas, Suhui Ye, Annett Braune, Claudio J. Villar, Felipe Lombó
Frontiers in Microbiology, 2024
Aromadendrin and taxifolin are two flavanonols (derived from the precursor naringenin) displaying diverse beneficial properties for humans. The carbon skeleton of these flavonoids may be transformed by the human gastrointestinal microbiota into other compounds, like auronols, which exert different and interesting biological activities. While research in flavonoids has become a certainly extensive field, studies about auronols are still scarce. In this work, different versions of the key plant enzyme for flavanonols biosynthesis, The flavanone 3-hydroxylase (F3H), has been screened for selecting the best one for the de novo production of these compounds in the bacterial factory Streptomyces albidoflavus UO-FLAV-004-NAR, a naringenin overproducer strain. This screening has rendered 2.6 μg/L of aromadendrin and 2.1 mg/L of taxifolin final production titers. Finally, the expression of the chalcone isomerase (CHI) from the gut bacterium Eubacterium ramulus has rendered a direct conversion (after feeding experiments) of 38.1% of (+)-aromadendrin into maesopsin and 74.6% of (+)-taxifolin into alphitonin. Moreover, de novo heterologous biosynthesis of 1.9 mg/L of alphitonin was accomplished by means of a co-culture strategy of a taxifolin producer S. albidoflavus and a CHI-expressing Escherichia coli, after the observation of the high instability of alphitonin in the culture medium. This study addresses the significance of culture time optimization and selection of appropriate enzymes depending on the desired final product. To our knowledge, this is the first time that alphitonin de novo production has been accomplished.
Metabolic engineering strategies for naringenin production enhancement in Streptomyces albidoflavus J1074
Suhui Ye, Patricia Magadán-Corpas, Álvaro Pérez-Valero, Claudio J. Villar, Felipe Lombó
Microbial Cell Factories, 2023
Background Naringenin is an industrially relevant compound due to its multiple pharmaceutical properties as well as its central role in flavonoid biosynthesis. Results On our way to develop Streptomyces albidoflavus J1074 as a microbial cell factory for naringenin production, we have significantly increased the yields of this flavanone by combining various metabolic engineering strategies, fermentation strategies and genome editing approaches in a stepwise manner. Specifically, we have screened different cultivation media to identify the optimal production conditions and have investigated how the additive feeding of naringenin precursors influences the production. Furthermore, we have employed genome editing strategies to remove biosynthetic gene clusters (BGCs) associated with pathways that might compete with naringenin biosynthesis for malonyl-CoA precursors. Moreover, we have expressed MatBC, coding for a malonate transporter and an enzyme responsible for the conversion of malonate into malonyl-CoA, respectively, and have duplicated the naringenin BGC, further contributing to the production improvement. By combining all of these strategies, we were able to achieve a remarkable 375-fold increase (from 0.06 mg/L to 22.47 mg/L) in naringenin titers. Conclusion This work demonstrates the influence that fermentation conditions have over the final yield of a bioactive compound of interest and highlights various bottlenecks that affect production. Once such bottlenecks are identified, different strategies can be applied to overcome them, although the efficiencies of such strategies may vary and are difficult to predict.
Metabolic engineering in Streptomyces albidoflavus for the biosynthesis of the methylated flavonoids sakuranetin, acacetin, and genkwanin
Álvaro Pérez-Valero, Suhui Ye, Patricia Magadán-Corpas, Claudio J. Villar, Felipe Lombó
Microbial Cell Factories, 2023
Flavonoids are important plant secondary metabolites showing antioxidant, antitumor, anti-inflammatory, and antiviral activities, among others. Methylated flavonoids are particularly interesting compared to non-methylated ones due to their greater stability and intestinal absorption, which improves their oral bioavailability. In this work we have stablished a metabolic engineered strain of Streptomyces albidoflavus with enhanced capabilities for flavonoid production, achieving a 1.6-fold increase in the biosynthesis of naringenin with respect to the parental strain. This improved strain, S. albidoflavus UO-FLAV-004, has been used for the heterologous biosynthesis of the methylated flavonoids sakuranetin, acacetin and genkwanin. The achieved titers of sakuranetin and acacetin were 8.2 mg/L and 5.8 mg/L, respectively. The genkwanin titers were 0.8 mg/L, with a bottleneck identified in this producing strain. After applying a co-culture strategy, genkwanin production titers reached 3.5 mg/L, which represents a 4.4-fold increase. To our knowledge, this study presents the first biosynthesis of methylated flavonoids in not only any Streptomyces species, but also in any Gram-positive bacteria.
Optimized De Novo Eriodictyol Biosynthesis in Streptomyces albidoflavus Using an Expansion of the Golden Standard Toolkit for Its Use in Actinomycetes
Patricia Magadán-Corpas, Suhui Ye, Álvaro Pérez-Valero, Patrick L. McAlpine, Paula Valdés-Chiara, Jesús Torres-Bacete, Juan Nogales, Claudio J. Villar, Felipe Lombó
International Journal of Molecular Sciences, 2023
Eriodictyol is a hydroxylated flavonoid displaying multiple pharmaceutical activities, such as antitumoral, antiviral or neuroprotective. However, its industrial production is limited to extraction from plants due to its inherent limitations. Here, we present the generation of a Streptomyces albidoflavus bacterial factory edited at the genome level for an optimized de novo heterologous production of eriodictyol. For this purpose, an expansion of the Golden Standard toolkit (a Type IIS assembly method based on the Standard European Vector Architecture (SEVA)) has been created, encompassing a collection of synthetic biology modular vectors (adapted for their use in actinomycetes). These vectors have been designed for the assembly of transcriptional units and gene circuits in a plug-and-play manner, as well as for genome editing using CRISPR-Cas9-mediated genetic engineering. These vectors have been used for the optimization of the eriodictyol heterologous production levels in S. albidoflavus by enhancing the flavonoid-3′-hydroxylase (F3’H) activity (by means of a chimera design) and by replacing three native biosynthetic gene clusters in the bacterial chromosome with the plant genes matBC (involved in extracellular malonate uptake and its intracellular activation into malonyl-CoA), therefore allowing more malonyl-CoA to be devoted to the heterologous production of plant flavonoids in this bacterial factory. These experiments have allowed an increase in production of 1.8 times in the edited strain (where the three native biosynthetic gene clusters have been deleted) in comparison with the wild-type strain and a 13 times increase in eriodictyol overproduction in comparison with the non-chimaera version of the F3′H enzyme.
Uncovering the Cryptic Gene Cluster ahb for 3-amino-4-hydroxybenzoate Derived Ahbamycins, by Searching SARP Regulator Encoding Genes in the Streptomyces argillaceus Genome
Suhui Ye, Brian Molloy, Ignacio Pérez-Victoria, Ignacio Montero, Alfredo F. Braña, Carlos Olano, Sonia Arca, Jesús Martín, Fernando Reyes, José A. Salas, Carmen Méndez
International Journal of Molecular Sciences, 2023
Combinatorial biosynthesis yields novel hybrid argimycin P alkaloids with diverse scaffolds in Streptomyces argillaceus
Suhui Ye, Giovanni Ballin, Ignacio Pérez‐Victoria, Alfredo F. Braña, Jesús Martín, Fernando Reyes, José A. Salas, Carmen Méndez
Microbial Biotechnology, 2022
Reconstruction of a genome-scale metabolic model of streptomyces albus j1074: Improved engineering strategies in natural product synthesis
Cheewin Kittikunapong, Suhui Ye, Patricia Magadán-Corpas, Álvaro Pérez-Valero, Claudio J. Villar, Felipe Lombó, Eduard J. Kerkhoven
Metabolites, 2021
Discovery of Cryptic Largimycins in Streptomyces Reveals Novel Biosynthetic Avenues Enriching the Structural Diversity of the Leinamycin Family
Adriana Becerril, Ignacio Pérez-Victoria, Suhui Ye, Alfredo F. Braña, Jesús Martín, Fernando Reyes, José A. Salas, Carmen Méndez
ACS Chemical Biology, 2020
Fine-tuning the regulation of Cas9 expression levels for efficient CRISPR-Cas9 mediated recombination in Streptomyces
Suhui Ye, Behnam Enghiad, Huimin Zhao, Eriko Takano
Journal of Industrial Microbiology and Biotechnology, 2020
Structure and Function of an Elongation Factor P Subfamily in Actinobacteria
Bruno Pinheiro, Christopher M. Scheidler, Pavel Kielkowski, Marina Schmid, Ignasi Forné, Suhui Ye, Norbert Reiling, Eriko Takano, Axel Imhof, Stephan A. Sieber, Sabine Schneider, Kirsten Jung
Cell Reports, 2020
New insights into the biosynthesis pathway of polyketide alkaloid argimycins P in Streptomyces argillaceus
Suhui Ye, Alfredo F. Braña, Javier González-Sabín, Francisco Morís, Carlos Olano, José A. Salas, Carmen Méndez
Frontiers in Microbiology, 2018
Identification by genome mining of a type I polyketide gene cluster from Streptomyces argillaceus involved in the biosynthesis of pyridine and piperidine alkaloids argimycins P
Suhui Ye, Brian Molloy, Alfredo F. Braña, Daniel Zabala, Carlos Olano, Jesús Cortés, Francisco Morís, José A. Salas, Carmen Méndez
Frontiers in Microbiology, 2017

Suhui Ye Huang

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Scopus Publications