Here we report the biosynthetic pathway for the neoantimycin and present three novel neoantimycin analogues, neoantimycin D (1), E (2) and F (3), from this assembly system from Streptoverticillium orinoci. Identification of these novel neoantimycin variants was achieved by selective MS/MS interrogation of natural product extracts using diagnostic fragments of the known neoantimycins. Their structures, including the absolute configurations, were elucidated using a combination of NMR experiments, detailed MS/MS experiments and the advanced Marfey's method. The biosynthetic pathway of neoantimycin was dissected by genome sequencing data analysis for the first time, which includes a hybrid nonribosomal peptide synthetase (NRPS) and polyketide synthetase (PKS) assembly lines.
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http://dx.doi.org/10.1016/j.bmcl.2013.07.031 | DOI Listing |
Org Lett
March 2025
National Center for Natural Products Research, School of Pharmacy, University of Mississippi, University, Mississippi 38677, United States.
Astracondensatol D (), a pentacyclic triterpenoid featuring an uncommon 6/6/5/6-fused ring system, along with its precursor astracondensatol E (), and two simplified 20(27)-octanorcycloastragenol derivatives ( and ) were isolated from for the first time. Classical NMR spectroscopic data, integrated with NMR and DP4+ calculations, unambiguously determined their absolute stereostructures. X-ray crystallography provided independent confirmation of the structure of compound .
View Article and Find Full Text PDFBioresour Bioprocess
March 2025
Key Laboratory of Bioorganic Synthesis of Zhejiang Province, College of Biotechnology and Bioengineering, Zhejiang University of Technology, No. 18, Chaowang Road, Hangzhou, Zhejiang Province, 310014, P. R. China.
S-adenosyl-L-methionine (SAM) is an important compound with significant pharmaceutical and nutraceutical applications. Currently, microbial fermentation is dominant in SAM production, which remains challenging due to its complex biosynthetic pathway and insufficient precursor availability. In this study, a multimodule engineering strategy based on CRISPR/Cas9 was established to improve the SAM productivity of Saccharomyces cerevisiae.
View Article and Find Full Text PDFMol Microbiol
March 2025
Department of Restorative Dentistry, School of Dentistry, Oregon Health and Science University, Portland, Oregon, USA.
MecA is a broadly conserved adaptor protein in Gram-positive bacteria, mediating the recognition and degradation of specific target proteins by ClpCP protease complexes. MecA binds target proteins, often through recognition of degradation tags or motifs, and delivers them to the ClpC ATPase, which unfolds and translocates the substrates into the ClpP protease barrel for degradation. MecA activity is tightly regulated through interactions with ClpC ATPase and other factors, ensuring precise control over protein degradation and cellular homeostasis.
View Article and Find Full Text PDFBiotechnol Biofuels Bioprod
March 2025
Institute of Chemical, Environmental and Bioscience Engineering, TU Wien, 1060, Vienna, Austria.
Background: Given the global rise in antimicrobial resistance, the discovery of novel antimicrobial agents and production processes thereof are of utmost importance. To this end we have activated the gene cluster encoding for the biosynthesis of the potent antifungal compound ilicicolin H in the fungus Trichoderma reesei. While the biosynthetic gene cluster (BGC) is silent under standard cultivation conditions, we achieved BGC activation by genetically overexpressing the transcription factor TriliR.
View Article and Find Full Text PDFMicrob Cell Fact
March 2025
Key Laboratory of Agricultural Environmental Microbiology, Ministry of Agriculture; Microbiology Department, College of Life Sciences, Nanjing Agricultural University, Nanjing, Jiangsu, 210095, China.
Background: Ganoderic acids (GAs), recognized as significant triterpenoid bioactive components in Ganoderma lucidum, exhibit a broad spectrum of pharmacological activities, including immunomodulation, anti-cancer, and anti-aging properties. Despite their significant pharmacological potential, the low yield of GAs from natural sources has emerged as a critical bottleneck hindering their broader application in the pharmaceutical and health care industries. Previous studies have suggested that environmental perturbations can influence energy metabolism, potentially impacting the biosynthesis of bioactive compounds.
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