Chemical probes capable of reacting with KS (ketosynthase)-bound biosynthetic intermediates were utilized for the investigation of the model type I iterative polyketide synthase 6-methylsalicylic acid synthase (6-MSAS) in vivo and in vitro. From the fermentation of fungal and bacterial 6-MSAS hosts in the presence of chain termination probes, a full range of biosynthetic intermediates was isolated and characterized for the first time. Meanwhile, in vitro studies of recombinant 6-MSA synthases with both nonhydrolyzable and hydrolyzable substrate mimics have provided additional insights into substrate recognition, providing the basis for further exploration of the enzyme catalytic activities.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4950124 | PMC |
| http://dx.doi.org/10.1002/ange.201509038 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Genomic Features of and the Transcriptional Regulation of Secondary Metabolite Biosynthesis.
J Fungi (Basel)
November 2024
College of Biological and Food Engineering, Southwest Forestry University, Kunming 650224, China.
Fungal secondary metabolites (SMs) have broad applications in biomedicine, biocontrol, and the food industry. In this study, whole-genome sequencing and annotation of were conducted, followed by comparative genomic analysis with 11 other species of Polyporales to examine genomic variations and secondary metabolite biosynthesis pathways. Additionally, transcriptome data were used to analyze the differential expression of polyketide synthase (PKS), terpene synthase (TPS) genes, and transcription factors (TFs) under different culture conditions.
View Article and Find Full Text PDFEngineering a carbon source-responsive promoter for improved biosynthesis in the non-conventional yeast .
Metab Eng Commun
June 2024
Department of Chemical & Biomolecular Engineering, University of California, Irvine, CA, 92697-2580, USA.
Many desired biobased chemicals exhibit a range of toxicity to microbial cell factories, making industry-level biomanufacturing more challenging. Separating microbial growth and production phases is known to be beneficial for improving production of toxic products. Here, we developed a novel synthetic carbon-responsive promoter for use in the rapidly growing, stress-tolerant yeast , by fusing carbon-source responsive elements of the native promoter to the strong or native promoter cores.
View Article and Find Full Text PDFFirst-class - biosynthesis of 6-MSA and bostrycoidin type I polyketides in .
Front Fungal Biol
March 2024
Department of Chemistry and Bioscience, Aalborg University, Esbjerg, Denmark.
Fungal polyketides are a large group of secondary metabolites, valuable due to their diverse spectrum of pharmacological activities. Polyketide biosynthesis in filamentous fungi presents some challenges: small yield and low-purity titers. To tackle these issues, we switched to the yeast , an easily cultivable heterologous host.
View Article and Find Full Text PDF6-MSA, a secondary metabolite distribution hub with multiple fungal destinations.
J Appl Microbiol
June 2023
Department of Chemistry and Bioscience, Aalborg University, Esbjerg, 6700, Denmark.
6-methylsalicylic acid (6-MSA) is a small, simple polyketide produced by a broad spectrum of fungal species. Since fungi obtained the ability to synthesize 6-MSA from bacteria through a horizontal gene transfer event, it has developed into a multipurpose metabolic hub from where numerous complex compounds are produced. The most relevant metabolite from a human perspective is the small lactone patulin as it is one of the most potent mycotoxins.
View Article and Find Full Text PDFStructural Insight of KSIII (β-Ketoacyl-ACP Synthase)-like Acyltransferase ChlB3 in the Biosynthesis of Chlorothricin.
Molecules
September 2022
State Key Laboratory of Microbial Metabolism and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.
Chlorothricin (CHL) belongs to a spirotetronate antibiotic family produced by that inhibits pyruvate carboxylase and malate dehydrogenase. For the biosynthesis of CHL, ChlB3 plays a crucial role by introducing the 6-methylsalicylic acid (6MSA) moiety to ChlB2, an acyl carrier protein (ACP). However, the structural insight and catalytic mechanism of ChlB3 was unclear.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!