Engineering modular polyketide synthases (PKSs) has the potential to be an effective methodology to produce existing and novel chemicals. However, this potential has only just begun to be realized. We propose the adoption of an iterative design-build-test-learn paradigm to improve PKS engineering. We suggest methods to improve engineered PKS design by learning from laboratory-based selection; adoption of DNA design software and automation to build constructs and libraries more easily; tools for the expression of engineered proteins in a variety of heterologous hosts; and mass spectrometry-based high-throughput screening methods. Finally, lessons learned during iterations of the design-build-test-learn cycle can serve as a knowledge base for the development of a single retrosynthesis algorithm usable by both PKS experts and non-experts alike.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.copbio.2014.04.011 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Genome Sequencing and Metabolic Potential Analysis of .
J Fungi (Basel)
December 2024
Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
is an edible and medicinal macrofungus with significant biological activity and broad pharmaceutical prospects that has received increasing attention in recent years. Although it is an important resource for macrofungi, knowledge of it remains limited. In this study, we sequenced, de novo assembled, and annotated the whole genome of using a PacBio Sequel II sequencer.
View Article and Find Full Text PDFd-Galactose-Esterification of a Fungal Polyketide Catalyzed by a Carnitine Acyltransferase Domain.
Chembiochem
December 2024
University of California Los Angeles, Dept. of Chemical And Biomolecular Engineering, 5531 Boelter Hall, 420 Westwood Plaza, 90095, Los Angeles, UNITED STATES OF AMERICA.
While sugar-containing natural products are commonly biosynthesized via glycosyltranferases using sugar-UDP as the electrophile, nature has evolved alternative strategies of glyco-modification to expand the diversity of natural products. Hydroxyl groups on sugars can serve as nucleophiles in the release of polyketide products from polyketide synthases. Herein, we demonstrate a highly reducing polyketide synthase (HRPKS) from the biocontrol fungus Trichoderma afroharzianum T22, which is terminated with a carnitine acyltransferase (cAT) domain, catalyzes the biosynthesis of a d-galactose esterified polyketide named as trichogalactin.
View Article and Find Full Text PDFStructure-based development of N-Arylindole derivatives as Pks13 inhibitors against Mycobacterium tuberculosis.
Eur J Med Chem
February 2025
Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, 3663 North Zhongshan Road, Shanghai, 200062, China. Electronic address:
Targeting the biosynthetic pathway of mycolic acid is highly attractive to researchers in the field of novel anti-tubercular drug development. Pks13-TE is an essential catalytic component in the last assembling step of mycolic acid, and the co-crystal structures of the Pks13-TE-inhibitor complex provide insight into ligand recognition. Based on a structure-guided strategy, N-aryl indole derivatives were designed, synthesized, and evaluated for their antitubercular activities.
View Article and Find Full Text PDFIdentification and Reconstitution of the First Two Enzymatic Steps for the Biosynthesis of Bioactive Meroterpenoids from (Lion's Mane Mushroom).
Molecules
November 2024
Department of Chemical and Pharmaceutical Biology, Groningen Research Institute of Pharmacy, University of Groningen, 9713 AV Groningen, The Netherlands.
(Lion's Mane mushroom) is widely consumed for its numerous reported benefits for brain health. A growing body of evidence suggests that these benefits are likely attributable to aromatic compounds contained in its fruiting bodies, including the meroterpenoids hericenones. Here, we report the identification and reconstitution of the first two steps of the biosynthetic pathway of hericenones via heterologous expression of the polyketide synthase HerA and the carboxylic acid reductase HerB in .
View Article and Find Full Text PDFGiant Polyketide Synthases Biosynthesize a Marine Polyether Biotoxin.
Angew Chem Int Ed Engl
December 2024
Institute of Pharmaceutical Sciences, Albert-Ludwigs-Universität Freiburg, Albertstrasse 25, 79194, Freiburg.
Prymnesin toxins were probably the direct cause of the environmental catastrophe in the Oder river in 2022. They belong to the so-called ladder polyethers, which are among the most toxic non-proteinogenic substances and have caused a whole series of food poisoning in humans and numerous other incidents of fish deaths. Despite massive efforts, the enzymatic machinery has remained enigmatic.
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!