Production of non-natural 5-methylorsellinate-derived meroterpenoids in Aspergillus oryzae
In this study, we constructed engineered metabolic pathways in the fungus Aspergillus oryzae to expand the molecular diversity of meroterpenoids. We employed the 5-methylorsellinic acid (5-MOA) synthase FncE and three additional biosynthetic enzymes for the formation of (6R,10′R)-epoxyfarnesyl-5-MOA methyl ester, which served as a non-native substrate for four terpene cyclases from DMOA-derived meroterpenoid pathways. As a result, we successfully generated six unnatural 5-MOA-derived meroterpenoid species, demonstrating the effectiveness of our approach in the generation of structural analogues of meroterpenoids. Be...
Source: Beilstein Journal of Organic Chemistry - March 20, 2024 Category: Chemistry Authors: Beilstein Journal of Organic Chemistry - Syndicated Feeds Tags: biosynthesis meroterpenoids natural products pathway engineering terpene cyclases Letter Source Type: research

The dynamics of the flavin, NADPH, and active site loops determine the mechanism of activation of class B flavin ‐dependent monooxygenases
AbstractFlavin-dependent monooxygenases (FMOs) constitute a diverse enzyme family that catalyzes crucial hydroxylation, epoxidation, and Baeyer –Villiger reactions across various metabolic pathways in all domains of life. Due to the intricate nature of this enzyme family's mechanisms, some aspects of their functioning remain unknown. Here, we present the results of molecular dynamics computations, supplemented by a bioinformatics analysis , that clarify the early stages of their catalytic cycle. We have elucidated the intricate binding mechanism of NADPH and L-Orn to a class B monooxygenase, the ornithine hydroxylase fro...
Source: Protein Science - March 19, 2024 Category: Biochemistry Authors: Gustavo Pierdominici ‐Sottile, Juliana Palma, María Leticia Ferrelli, Pablo Sobrado Tags: RESEARCH ARTICLE Source Type: research

The role of the Flb protein family in the life cycle of Aspergillus niger
Antonie Van Leeuwenhoek. 2024 Mar 19;117(1):58. doi: 10.1007/s10482-024-01957-x.ABSTRACTGenes flbA-E are involved in sporulation and vegetative growth in Aspergillus nidulans. Inactivation of either of these genes results in a fluffy phenotype with delayed or even abolished sporulation. Previously, a non-sporulating phenotype was obtained by inactivating flbA in Aspergillus niger, which was accompanied by lysis, thinner cell walls, and an increased secretome complexity. Here, we further studied the role of the flb genes of A. niger. Strains ΔflbA, ΔflbB and ΔflbE showed increased biomass formation, while inactivation of...
Source: Antonie van Leeuwenhoek - March 19, 2024 Category: Microbiology Authors: Xiaoyi Chen Juan P Moran Torres Han A B W östen Source Type: research

Protein disulfide isomerase 1 is required for RodA assembling-based conidial hydrophobicity of < em > Aspergillus fumigatus < /em >
In conclusion, Pdi1 ensures the correct folding of RodA in the inner layer of conidia, facilitating its secretion into the outer layer of the cell wall and allowing self-assembly of the hydrophobic layer. This study has identified a regulatory element for conidia rodlet assembly.IMPORTANCEAspergillus fumigatus is the major cause of invasive aspergillosis, which is mainly transmitted by the inhalation of conidia. The spread of conidia is largely dependent on their hydrophobicity, which is primarily attributed to the self-assembly of the hydrophobic protein RodA on the cell wall. However, the mechanisms underlying RodA secre...
Source: Applied and Environmental Microbiology - March 19, 2024 Category: Microbiology Authors: Xiaotao Hu Yao Zhou Renning Liu Jing Wang Lingyan Guo Xiaofei Huang Jingyi Li Yunfeng Yan Feiyun Liu Xueying Li Xinyu Tan Yiqing Luo Ping Wang Shengmin Zhou Source Type: research

PCR diagnostic platforms for non- < em > Aspergillus < /em > mold infections: ready for routine implementation in the clinic?
Expert Rev Mol Diagn. 2024 Mar 19:1-10. doi: 10.1080/14737159.2024.2326474. Online ahead of print.ABSTRACTINTRODUCTION: While Aspergillus spp. remain the predominant cause of invasive mold infections, non-Aspergillus molds, such as the Mucorales or Fusarium spp., account for an increasing proportion of cases. The diagnosis of non-Aspergillus invasive mold infections (NAIMI) is challenging because of the low sensitivity and delay of conventional microbiological tests. Therefore, there is a particular interest to develop molecular tools for their early detection in blood or other clinical samples.AREAS COVERED: This extensiv...
Source: Expert Review of Molecular Diagnostics - March 19, 2024 Category: Laboratory Medicine Authors: Frederic Lamoth Dimitrios P Kontoyiannis Source Type: research