Biosynthesis of Natural and Unnatural Perylenequinones for Drug Development DOI
Zengping Su, Yan Zhang, Zhenbo Yuan

и другие.

ChemMedChem, Год журнала: 2024, Номер 19(20)

Опубликована: Июнь 29, 2024

A wide range of perylenequinones (PQs) with diverse structures and versatile bioactivities have long been isolated, positioning them as highly promising agents for photodynamic therapy (PDT). However, the lack an efficient cost-effective method to obtain these compounds introduce structural diversity complexity currently hinders their further research application. In this concept, we present a comprehensive overview advancements in biosynthetic pathways natural PQs based on classification, also summarize recent progress biosynthesis derivatives. These pioneering efforts may pave way structure modification large-scale bioproduction unnatural through synthetic biology strategies promote drug development.

Язык: Английский

What can reactive oxygen species (ROS) tell us about the action mechanism of herbicides and other phytotoxins? DOI

Valeria A. Dmitrieva,

Elena V. Tyutereva, Olga V. Voitsekhovskaja

и другие.

Free Radical Biology and Medicine, Год журнала: 2024, Номер 220, С. 92 - 110

Опубликована: Апрель 23, 2024

Язык: Английский

Процитировано

9

Synthetic Biology‐based Construction of Unnatural Perylenequinones with Improved Photodynamic Anticancer Activities DOI
Zengping Su, Baodang Guo, Huibin Xu

и другие.

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(11)

Опубликована: Янв. 23, 2024

Abstract The construction of structural complexity and diversity natural products is crucial for drug discovery development. To overcome high dark toxicity poor photostability photosensitizer perylenequinones (PQs) photodynamic therapy, herein, we aim to introduce the biosynthesize desired unnatural PQs in fungus Cercospora through synthetic biology‐based strategy. Thus, first elucidate intricate biosynthetic pathways class B reveal how branching enzymes create their from a common ancestor. This enables rational reprogramming cercosporin pathway generate diverse without chemical modification. Among them, A displays remarkably low with retention great anticancer antimicrobial activities. Moreover, it found that, unlike cercosporin, could be selectively accumulated cancer cells, providing potential targets Therefore, this work provides comprehensive foundation preparing customized functions strategies, thus facilitating pipelines nature.

Язык: Английский

Процитировано

8

Alternaria alternata Isolated from Infected Pears (Pyrus communis) in Italy Produces Non-Host Toxins and Hydrolytic Enzymes as Infection Mechanisms and Exhibits Competitive Exclusion against Botrytis cinerea in Co-Infected Host Fruits DOI Creative Commons
Stefany Castaldi, Jesús G. Zorrilla, Claudia Petrillo

и другие.

Journal of Fungi, Год журнала: 2023, Номер 9(3), С. 326 - 326

Опубликована: Март 7, 2023

Alternaria alternata is one of the most devastating phytopathogenic fungi. This microorganism causes black spots in many fruits and vegetables worldwide, generating significant post-harvest losses. In this study, an A. strain, isolated from infected pears (Pyrus communis) harvested Italy, was characterized by focusing on its pathogenicity mechanisms competitive exclusion presence another pathogen, Botrytis cinerea. vitro assays, fungus produces strong enzymatic activities such as amylase, xylanase, cellulase, potentially involved during infection. Moreover, it secretes four different toxins purified identified altertoxin I, alteichin, alternariol, alternariol 4-methyl ether. Only alteichin generated necrotic lesions host-variety pears, while all compounds showed moderate to slight activity non-host other fruit (lemon, Citrus limon), indicating they are toxins. Interestingly, has shown competitor cinerea when co-inoculated host pear fruits, inhibiting growth 70 65%, respectively, a result not observed preliminary characterization dual culture assay. Alteichin ether tested against B. had best inhibition activity, suggesting that synergism these probably dynamics fruits.

Язык: Английский

Процитировано

10

Industrial Production of Antibiotics in Fungi: Current State, Deciphering the Molecular Basis of Classical Strain Improvement and Increasing the Production of High-Yielding Strains by the Addition of Low-Molecular Weight Inducers DOI Creative Commons
Alexander A. Zhgun

Fermentation, Год журнала: 2023, Номер 9(12), С. 1027 - 1027

Опубликована: Дек. 16, 2023

The natural fermentation of antibiotics, along with semi-synthetic and synthetic approaches, is one the most important methods for their production. majority antibiotic market comes from high-yielding (HY) fungal strains. These strains have been obtained since 1950s wild-type (WT) isolates as a result classical strain improvement (CSI) programs primarily involving multi-round random mutagenesis screening. However, molecular basis leading to high-yield production was unknown. In recent years, due application multiomic key changes that occur in CSI programs, WT become HY industrial producers particular antibiotic, begun be understood. It becomes obvious that, during CSI, certain universal events are selected, which lead both direct increase target metabolite affect other vital processes cell (side mutations). include: upregulation biosynthetic gene cluster (BGC), system global regulation, disruption alternative BGCs, rearrangement energy fluxes favor SM (secondary metabolite), regulation response stress, redirection primary metabolic pathways obtain more precursors This knowledge opens up possibility introducing targeted using genetic engineering when creating new increasing low-molecular compounds, compensate effects side mutations.

Язык: Английский

Процитировано

9

Nitric oxide mediates red light-induced perylenequinone production in Shiraia mycelium culture DOI Creative Commons

Wen Juan Wang,

Xin Ping Li,

Wen Hao Shen

и другие.

Bioresources and Bioprocessing, Год журнала: 2024, Номер 11(1)

Опубликована: Янв. 2, 2024

Abstract Perylenequinones (PQs) from bambusicolous Shiraia fungi serve as excellent photosensitizers for photodynamic therapy. However, the lower yield of PQ production in mycelium cultures is an important bottleneck their clinical application. Light has long been recognized a pivotal regulatory signal fungal secondary metabolite biosynthesis. In this study, we explored role nitric oxide (NO) growth and biosynthesis sp. S9 exposed to red light. The continuous irradiation with light (627 nm, 200 lx) suppressed conidiation, promoted hyphal branching, elicited notable increase accumulation. Red exposure induced NO generation, peaking 81.7 μmol/g FW on day 8 culture, involvement synthase (NOS)- or nitrate reductase (NR)-dependent pathways. application donor sodium nitroprusside (SNP) restored conidiation under stimulated production, which was mitigated upon introduction scavenger carboxy-PTIO soluble guanylate cyclase inhibitor NS-2028. These results showed that light-induced NO, signaling molecule, involved regulation through NO-cGMP-PKG pathway. While mycelial H 2 O content exhibited no significant alternations, transient intracellular Ca 2+ extracellular ATP (eATP) detected generation found be interdependent cytosolic eATP concentration. molecules cooperated synergistically enhance membrane permeability elevate transcript levels biosynthetic genes S9. Notably, combined treatment 5 μM SNP yielded synergistic effect, resulting substantially higher level hypocrellin A (HA, 254 mg/L), about 3.0-fold over dark control. Our findings provide valuable insights into present promising strategy involving elicitation enhanced photoactive PQs other metabolites fungi. Graphical

Язык: Английский

Процитировано

3

Antifeedant, antifungal and nematicidal compounds from the endophyte Stemphylium solani isolated from wormwood DOI Creative Commons
Carmen E. Díaz, María Fe Andrés, Rodney Lacret

и другие.

Scientific Reports, Год журнала: 2024, Номер 14(1)

Опубликована: Июнь 12, 2024

The continuous search for natural product-based biopesticides from fungi isolated untapped sources is an effective tool. In this study, we studied a pre-selected fungal endophyte, isolate Aa22, the medicinal plant Artemisia absinthium, along with antifungal, insect antifeedant and nematicidal compounds present in extract. endophyte Aa22 was identified as Stemphylium solani by molecular analysis. antifungal activity tested broth microdilution against Fusarium solani, F. oxysporum, moniliforme Botrytis cinerea, choice bioassays Spodoptera littoralis, Myzus persicae Rhopalosiphum padi vitro mortality root-knot nematode Meloiydogyne javanica. structures of bioactive were determined on basis 1D 2D NMR spectroscopy mass spectrometry. ethyl acetate extract obtained solid rice fermentation showed mycelial growth inhibition pathogens (EC

Язык: Английский

Процитировано

3

Mitochondrial genome and transcription of Shiraia-like species reveal evolutionary aspects in protein-coding genes DOI Creative Commons
X. SHEN,

Xue-Ting Cao,

Xiao-Bo Huang

и другие.

IMA Fungus, Год журнала: 2025, Номер 16

Опубликована: Фев. 20, 2025

Shiraia-related species are well-known bambusicolous fungi in Dothideomycetes class, with high value traditional medicine for producing hypocrellin, as an anticipated photosensitiser. The complete mitogenomes of hypocrellin-producing Pseudoshiraiaconidialis strains were analysed the present study, functional gene variations through comparative genomics and transcriptomics. Five (ZZZ816, CNUCC1353PR, JAP103846, CNUCC C72, C151) sequenced, which indicated similar genome characteristics. Two them possess extra atp6 gene, associated variable fragment "HSP1-HSP2-atp6_2" correlates closely hypocrellin production capacity. Therefore, these five divided into three groups: ZZZ816 CNUCC1353PR possessing efficiency, C72 JAP103846 low yield C151 a transition type. expression changes screened under various conditions. ZZZ816-related showed significant mitochondrial genes, especially HSP1, HSP2 atp6_2, linked to synthesis stress response; rps3 also consistently correlated production. group stable pattern divergently, except suppression by blue light. These findings would provide new insights secondary metabolite regulation ROS resistance. Above all, this study conducted comprehensive analysis Shiraia-like expression, can update understanding fungal evolution potential improved

Язык: Английский

Процитировано

0

Production of the light-activated elsinochrome phytotoxin in the soybean pathogen Coniothyrium glycines hints at virulence factor DOI Creative Commons
Nicholas Greatens, Harun M. Murithi,

Danny Coyne

и другие.

PLoS ONE, Год журнала: 2025, Номер 20(5), С. e0321896 - e0321896

Опубликована: Май 13, 2025

The Dothideomycete pathogen Coniothyrium glycines causes red leaf blotch of soybean, a major disease in Africa. It is one two fungal plant pathogens on the USDA PPQ Select Agents and Toxins list important to biosecurity United States, reflective its potential be highly destructive if introduced. Despite importance, there are no published reports regarding molecular basis host infection. Examination C. genome revealed secondary metabolite gene cluster that similar content organization clusters synthesize light-activated perylenequinone toxins, such as cercosporin. Perylenequinones non-host specific toxins that, upon exposure light, generate reactive oxygen species, which have near-universal toxicity hosts. isolates from eastern southern Africa were cultured axenically under light dark conditions. Light-grown cultures produced red-pink pigmentation typical perylenequinones. Differential expression analysis showed six eight genes biosynthetic cluster, including polyketide synthase gene, significantly upregulated light. Liquid chromatography-mass spectrometry confirmed production elsinochrome A, known virulence factor other pathogens. On leaves incubated dark, fewer lesions formed symptoms delayed, compared In addition, we identified orthologous more distantly related where their presence was previously unknown, indicating broader importance these agriculture ecology. This work provides first evidence A may contribute .

Язык: Английский

Процитировано

0

Biotechnological production and potential applications of hypocrellins DOI

Zhuanying Bao,

Yunchang Xie,

Chenglong Xu

и другие.

Applied Microbiology and Biotechnology, Год журнала: 2023, Номер 107(21), С. 6421 - 6438

Опубликована: Сен. 11, 2023

Язык: Английский

Процитировано

8

Tailoring intersystem crossing of perylenediimide through chalcogen-substitution at bay-position: A theoretical perspective DOI
Raka Ahmed, Arun K. Manna

The Journal of Chemical Physics, Год журнала: 2022, Номер 157(21)

Опубликована: Ноя. 10, 2022

Molecular-scale design strategies for promoting intersystem crossing (ISC) in small organic molecules are ubiquitous developing efficient metal-free triplet photosensitizers with high quantum yield (ΦT). Air-stable and highly fluorescent perylenediimide (PDI) its pristine form displays very ISC compared to the fluorescence due large singlet-triplet gap (ΔES-T) negligibly spin-orbit coupling (SOC) between lowest singlet (S1) state (T1). However, ΦT can be tuned by different chemical mechanical means that capable of either directly lowering ΔES-T increasing SOC or introducing intermediate low-lying states (Tn, n = 2, 3, …) S1 T1. To this end, herein, a few chalcogen (X O, S, Se) bay-substituted PDIs (PDI-X2) computationally modeled aiming at geometrical-strain PDI core also mixing nπ* orbital character ππ* excited states, which altogether may reduce improve SOC. Our quantum-chemical calculations based on optimally range-separated hybrid reveal presence 3) T1 all three PDI-X2 studied dichloromethane. More importantly, shows significantly improved rate than combined effects stemming from smaller larger The calculated rates follow order as PDI-O2 < PDI-S2 PDI-Se2. These research findings will helpful designing biomedical, sensing, photonic applications.

Язык: Английский

Процитировано

12