Article
Plant Sciences
Yong Chen, Ying Jie Wei, Nan Jiang, Hui Ming Ge, Rui Hua Jiao, Xu Cheng, Ren Xiang Tan
Summary: A new antiosteoporotic compound, Spirocitromycetin, has been characterized and its structure and biosynthetic pathway have been elucidated. Furthermore, a novel antiosteoporotic pharmacophore has been identified.
JOURNAL OF NATURAL PRODUCTS
(2022)
Article
Chemistry, Organic
Kaijin Zhang, Guojian Zhang, Xuewen Hou, Chuanteng Ma, Junyu Liu, Qian Che, Tianjiao Zhu, Dehai Li
Summary: Prenyltransferase CdnC plays a crucial role in the construction of noncanonical chrodrimanin skeletons and can generate a series of novel chrodrimanin-like structures.
Article
Chemistry, Organic
Lin Chen, Jian-Wei Tang, Yan Yee Liu, Yudai Matsuda
Summary: Characterization of a biosynthetic gene cluster in the fungus Aspergillus candidus CBS 102.13 led to the discovery of a new alkaloid, aspcandine (1). The unique molecular scaffold of aspcandine (1) is synthesized by the nonribosomal peptide synthetase-polyketide synthase hybrid AcdB, which incorporates 3-hydroxy-L-kynurenine as a building block. AcdB performs chain elongation using malonyl-CoA and releases the chain to form the tricyclic system of aspcandine (1).
Article
Chemistry, Physical
Fei Cao, Wen-Tao Tao, Qian Yu, Chu-Xuan Xu, Jin-Tao Cheng, Ruo-Xi Liu, Qing-Wei Zhao, Xin-Hang Jiang, Yu Liu, Yong-Quan Li, Zha-Jun Zhan, Ting Shi, Xu-Ming Mao
Summary: This study identified two new semi-pinacolases from the epoxide hydrolase family, expanding the biocatalyst family for semipinacol rearrangement. Through comprehensive mutations and chemical calculations, critical residues were identified for the catalytic mechanisms of selective epoxide collapse and subsequent SPR.
Article
Chemistry, Multidisciplinary
Chris Rabot, Yuhao Chen, Swati Bijlani, Yi-Ming Chiang, C. Elizabeth Oakley, Berl R. Oakley, Travis J. Williams, Clay C. C. Wang
Summary: This article presents a novel chemical and biological approach for the rapid conversion of polyethylenes into structurally complex and pharmacologically active compounds. By engineering strains of the fungus Aspergillus nidulans, the authors have produced fungal secondary metabolites from the digestion products of polyethylenes, expanding the range of products to which polyethylenes can be upcycled.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Ying Huang, Sandra Hoefgen, Vito Valiante
Summary: This study elucidated the biosynthetic pathway of drimane-type sesquiterpene esters in fungi and identified key enzymes involved in the process. The findings deepen our understanding of how fungi synthesize drimane-type sesquiterpenes and corresponding esters.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Biotechnology & Applied Microbiology
Juanjuan Liu, Can Peng, Qiqi Han, Mengyao Wang, Gang Zhou, Bin Ye, Yazhong Xiao, Zemin Fang, Ursula Kuees
Summary: The study found that oxidative stress derived from antagonistic compounds secreted by Gongronella sp. w5 played a critical role in the production of laccase Lcc9 in Coprinopsis cinerea during fungal interactions. Lcc9 participates in a defense strategy to eliminate oxidative stress and promote cell growth and development. These findings deepen our understanding of fungal interactions in their natural population and communities.
APPLIED AND ENVIRONMENTAL MICROBIOLOGY
(2022)
Article
Engineering, Environmental
Daizong Cui, Jianqi Wang, He Wang, Yue Yang, Min Zhao
Summary: In this study, cadmium-based nanoparticles were biosynthesized using E. coli CD-2, with both Cd2+ and CdS NPs causing oxidative stress and affecting the cellular antioxidative system. The contents of Cd2+ and CdS NPs changed during the biosynthetic process, indicating the cells had to overexpress certain related genes to respond to the NPs-induced stress.
JOURNAL OF HAZARDOUS MATERIALS
(2021)
Article
Chemistry, Multidisciplinary
Shinji Kishimoto, Ayumi Minami, Yoshimitsu Aoki, Yuya Matsubara, Shogo Watanabe, Kenji Watanabe
Summary: Pathogenic fungi of Aspergillus section Fumigati are capable of producing various secondary metabolites. This study reports the isolation of fumimycin and a new compound named lentofuranine from A. lentulus. These compounds were found to be assembled through a nonenzymatic condensation involving a polyketide intermediate from the terrein biosynthetic pathway and a highly reactive azlactone intermediate. The formation of an unusual carbon skeleton is attributed to the reactivity of azlactone.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Organic
Zong-Hua Xiao, Jia-Yu Dong, Ao Li, Jia-Meng Dai, Yan-Ping Li, Qiu-Fen Hu, Li-Dong Shao, Yudai Matsuda, Wei-Guang Wang
Summary: In this study, using a cryptic gene cluster found in the fungus Aspergillus versicolor, researchers successfully synthesized and derived eight new analogues of fungal meroditerpenoids. Some of these analogues exhibited synergistic inhibition of MDA-MB-231 breast cancer cell viability when combined with the chemotherapeutic agent doxorubicin. This study expands our understanding of fungal meroditerpenoids and provides new candidate substances for further research on their biological activities and pharmacological effects.
ORGANIC CHEMISTRY FRONTIERS
(2022)
Article
Chemistry, Organic
Zong-Hua Xiao, Jia-Yu Don, Ao Li, Jia-Meng Dai, Yan-Ping Li, Qiu-Fen Hu, Li-Dong Shao, Yudai Matsuda, Wei-Guang Wang
Summary: Novel chevalone analogues with potential synergistic inhibition effects on breast cancer cells were synthesized by heterologously expressing a cryptic gene cluster found in fungi.
ORGANIC CHEMISTRY FRONTIERS
(2022)
Article
Multidisciplinary Sciences
Hongjiao Zhang, Zixin Li, Shuang Zhou, Shu-Ming Li, Huomiao Ran, Zili Song, Tao Yu, Wen-Bing Yin
Summary: FnsA is a novel NRPS-PKS hybrid that is involved in the formation of naringenin. It activates both p-coumaric acid and p-hydroxybenzoic acid through its adenylation domain and uses malonyl-CoA molecules for elongation. Refactoring the biosynthetic pathway with fnsA in yeast provides an alternative approach for the production of flavonoids such as isorhamnetin and acacetin.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Multidisciplinary
Lang Xiang, Jing Shi, Ao Zhu, Zi Fei Xu, Shuang He Liu, Yi Shuang Wang, Zhi Kai Guo, Rui Hua Jiao, Ren Xiang Tan, Hui Ming Ge
Summary: In this study, novel mutaxanthene analogues were discovered and the biosynthesis of these aromatic polyketides and their unusual xanthene framework was investigated. The complete biosynthetic pathway of mutaxathene was determined through gene deletion and biochemical experiments. A multifunctional FPMO, MtxO4, was found to catalyze ring rearrangement and generate the required xanthene ring. The total biosynthesis of mutaxanthene was successfully achieved in vitro. Our results reveal the formation of a rare xanthene ring in type II polyketide biosynthesis and demonstrate the potential of using total biosynthesis for the discovery of natural products synthesized by type II PKSs.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Organic
Li Rao, Hu-Cheng Shi, Yi Zou
Summary: A new fungal nonribosomal peptide-polyketide hybrid synthase, named CogA, was discovered through genome mining from fungus Cordyceps gunnii. Its ability to synthesize 4-hydroxyl 2-pyrrolidinone alkaloid (1) through nonenzyme-catalyzed N-1-C-2 closure was confirmed by heterologous expression in Aspergillus nidulans. Furthermore, the engineered biosynthesis of fluoro-substituted 2-pyrrolidinone alkaloid analogues (4 and 5) has also been achieved in vivo.
Article
Cell Biology
Silvia Magalhaes-Novais, Jan Blecha, Ravindra Naraine, Jana Mikesova, Pavel Abaffy, Alena Pecinova, Mirko Milosevic, Romana Bohuslavova, Jan Prochazka, Shawez Khan, Eliska Novotna, Radek Sindelka, Radek Machan, Mieke Dewerchin, Erik Vlcak, Joanna Kalucka, Sona Stemberkova Hubackova, Ales Benda, Jermaine Goveia, Tomas Mracek, Cyril Barinka, Peter Carmeliet, Jiri Neuzil, Katerina Rohlenova, Jakub Rohlena
Summary: Mitochondrial oxidative phosphorylation (OXPHOS) not only generates ATP, but also supports autophagy to provide resistance against oxidative stress during cell quiescence.
Article
Chemistry, Organic
Kevin Becker, Eric Kuhnert, Russell J. Cox, Frank Surup
Summary: New stromatal azaphilone pigments, rubiginosins Z-X and rubiginosins Z and W, were isolated from two fungi with cytotoxic and antimicrobial activities. The structures were linked to putative biosynthetic gene clusters, revealing the mechanism of OA-substituted azaphilone synthesis in the fungi.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Microbiology
Mary L. Shenouda, Maria Ambilika, Elizabeth Skellam, Russell J. Cox
Summary: Trichoderma reesei has been developed as a microbial cell factory for the heterologous expression of fungal secondary metabolites. By inactivating sorbicillinoid biosynthesis and constructing vectors for the rapid cloning and expression of heterologous fungal biosynthetic genes, this strain can produce desired natural products on waste materials. This new method provides a way to convert waste biomass into secondary metabolites.
Review
Microbiology
Lei Li, Russell J. Cox
Summary: This review provides an overview of the known structures, biological activities, and biosynthetic pathways of the tropolone sesquiterpenoid family of fungal secondary metabolites. The synthesis of this knowledge enables the revision of likely structural and stereochemical misassignments and demonstrates the division of these compounds into three main biosynthetic classes based on the stereochemistry of key biosynthetic steps.
Review
Biochemistry & Molecular Biology
Russell J. Cox
Summary: Investigations over the past two decades have provided insights into the programming of fungal iterative highly-reducing polyketide synthases. Both in vitro and in vivo experiments have revealed the interaction between intrinsic and extrinsic selectivity of the catalytic domains in these systems. Structural biology has started to provide high resolution structures of hr-PKS that can be utilized for their engineering, although progress in this field is still at an early stage. However, there are significant opportunities to use the current understanding to reengineer these efficient systems for the production of important biologically active compounds through biotechnology.
NATURAL PRODUCT REPORTS
(2023)
Editorial Material
Biochemistry & Molecular Biology
Russell J. J. Cox, Tobias A. M. Gulder
Summary: Filamentous fungi are highly diverse eukaryotes that inhabit all known ecosystems on earth, with an estimated existence of over 2 x 106 species. They have vast biosynthetic potential, producing various secondary metabolites and hybrid compounds. These metabolites have significant medicinal uses, including antibiotics and antimicrobial agents. Fungi have evolved unique biosynthetic systems over billions of years.
NATURAL PRODUCT REPORTS
(2023)
Review
Biochemistry & Molecular Biology
Katherine Williams, Agnieszka J. Szwalbe, Kate M. J. De Mattos-Shipley, Andy M. Bailey, Russell J. Cox, Christine L. Willis
Summary: This review provides an overview of the discovery, structural elucidation, and recent advances in the bioactivity studies of Maleidrides compounds. Maleidrides possess significant pharmaceutical and agrochemical activities, and their unusual biosynthetic pathways have fascinated scientists for decades.
NATURAL PRODUCT REPORTS
(2023)
Article
Chemistry, Multidisciplinary
Yunlong Sun, Dongsong Tian, Eric Kuhnert, Geraldine Le Goff, Guillaume Arcile, Jamal Ouazzani, Russell J. Cox
Summary: This study investigates the fungal biosynthetic pathways of fungal tetraketide pyrones and provides insights into their synthesis, offering a platform for the total biosynthesis of this class of metabolites.
CHEMICAL COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
Henrike Heinemann, Kevin Becker, Hedda Schrey, Haoxuan Zeng, Marc Stadler, Russell J. Cox
Summary: Submerged cultivation results in the formation of new sulfur-containing sporothriolide derivatives, which show attenuated antimicrobial activity due to the presence of 2-hydroxy-3-mercaptopropanoic acid. However, these derivatives still exhibit moderate effects on the biofilms of Candida albicans and Staphylococcus aureus at lower concentrations.
Article
Chemistry, Organic
Juan He, Wei-Wei Yu, Masahiko Isaka, Russell J. Cox, Ji-Kai Liu, Tao Feng
Summary: Antroxazole A (1), a chamigrane type sesquiterpene dimer containing an oxazole moiety, was isolated from cultures of the fungus Antrodiella albocinnamomea. It exhibited specific inhibition against LPS-induced proliferation of B lymphocyte cells.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2022)
Article
Chemistry, Organic
Houchao Xu, Carsten Schotte, Russell J. Cox, Jeroen S. Dickschat
Summary: The non-canonical fungal alpha-humulene synthase was studied in terms of its stereochemical processes with isotopic labelling experiments. A new desymmetrisation strategy was developed to allow for a full stereochemical analysis from stereoselectively labelled farnesyl diphosphate to the achiral alpha-humulene product.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2021)
Article
Mycology
Ole Christian Hagestad, Lingwei Hou, Jeanette H. Andersen, Espen H. Hansen, Bjorn Altermark, Chun Li, Eric Kuhnert, Russell J. Cox, Pedro W. Crous, Joseph W. Spatafora, Kathleen Lail, Mojgan Amirebrahimi, Anna Lipzen, Jasmyn Pangilinan, William Andreopoulos, Richard D. Hayes, Vivian Ng, Igor Grigoriev, Stephen A. Jackson, Thomas D. S. Sutton, Alan D. W. Dobson, Teppo Rama
Summary: This study characterized the genomes of three marine fungi and identified their phylogenetic placement, biosynthetic potential, and carbohydrate active enzymes. The findings provide a valuable resource for further investigations on ecological adaptations of fungi using comparative genomics.
Article
Chemistry, Multidisciplinary
Sen Yin, Steffen Friedrich, Vjaceslavs Hrupins, Russell J. Cox
Summary: The study found that the enzymes involved in the biosynthesis of maleidrides from polyketides in fungi are closely related to primary metabolism enzymes of the citric acid cycle, but have expanded substrate selectivity. A key citrate synthase can react with both saturated and unsaturated acyl CoA substrates to produce solely anti-substituted citrates. This anti-dehydration reaction leads to the formation of an unsaturated precursor which is cyclized by ketosteroid-isomerase-like enzymes in vitro to produce byssochlamic acid.
Editorial Material
Chemistry, Multidisciplinary
Laura Fisher, Russell Cox
Article
Chemistry, Organic
James W. Marshall, Kate M. J. de Mattos-Shipley, Iman A. Y. Ghannam, Asifa Munawar, Jonathan C. Killen, Colin M. Lazarus, Russell J. Cox, Christine L. Willis, Thomas J. Simpson
Summary: Fusarochromene isolated from Fusarium sacchari is closely related to various mycotoxins, including fusarochromanone. Despite being assumed to be biosynthesized via polyketide pathway, experiments have shown that fusarochromene is unexpectedly derived from oxidative cleavage of tryptophan. A putative biosynthetic gene cluster has been identified.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2021)
Review
Chemistry, Multidisciplinary
Mary L. Shenouda, Russell J. Cox
Summary: Members of the genus Trichoderma have attracted widespread attention due to their efficient protein production capabilities and biocontrol activities, yet the study of their active metabolites and biosynthetic gene clusters has only recently gained significant attention. The challenges and opportunities in utilizing the full potential of Trichoderma spp. for natural product production, along with new metabolic engineering strategies, are discussed in this review.
