ArticleProceedings of the National Academy of Sciences of the United States of America2014
Diversity-oriented combinatorial biosynthesis of benzenediol lactone scaffolds by subunit shuffling of fungal polyketide synthases.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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31 citing papers in PubMed, 74 citations in OpenAlex.
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- Combinatorial biosynthesis for the engineering of novel fungal natural products.Communications chemistry · 2024Review
- Biosynthesis of Cytosporones in Leotiomycetous Filamentous Fungi.Journal of the American Chemical Society · 2024Article
- Engineered and total biosynthesis of fungal specialized metabolites.Nature reviews. Chemistry · 2024Review
- High-Titer Production of Olivetolic Acid and Analogs in Engineered Fungal Host Using a Nonplant Biosynthetic Pathway.ACS synthetic biology · 2021Article
- Saccharomyces cerevisiae as host for the recombinant production of polyketides and nonribosomal peptides.Microbial cell factories · 2021Review
- Combinatorial Biosynthesis of Sulfated Benzenediol Lactones with a Phenolic Sulfotransferase from Fusarium graminearum PH-1.mSphere · 2020Article
- Intrinsic and Extrinsic Programming of Product Chain Length and Release Mode in Fungal Collaborating Iterative Polyketide Synthases.Journal of the American Chemical Society · 2020Article
- Probing Selectivity and Creating Structural Diversity Through Hybrid Polyketide Synthases.Angewandte Chemie (International ed. in English) · 2020Article
- Synthetic biology based construction of biological activity-related library of fungal decalin-containing diterpenoid pyrones.Nature communications · 2020Article
- Genetic platforms for heterologous expression of microbial natural products.Natural product reports · 2019Review
- Rational Reprogramming of O-Methylation Regioselectivity for Combinatorial Biosynthetic Tailoring of Benzenediol Lactone Scaffolds.Journal of the American Chemical Society · 2019Article
- Methylglucosylation of aromatic amino and phenolic moieties of drug-like biosynthons by combinatorial biosynthesis.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- An unusual intramolecularTetrahedron · 2016Article
- Article
- Saccharomyces cerevisiae as a tool for mining, studying and engineering fungal polyketide synthases.Fungal genetics and biology : FG & B · 2016Review
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10 authors at 3 institutions in 2 countries.
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Abstract
Combinatorial biosynthesis aspires to exploit the promiscuity of microbial anabolic pathways to engineer the synthesis of new chemical entities. Fungal benzenediol lactone (BDL) polyketides are important pharmacophores with wide-ranging bioactivities, including heat shock response and immune system modulatory effects. Their biosynthesis on a pair of sequentially acting iterative polyketide synthases (iPKSs) offers a test case for the modularization of secondary metabolic pathways into "build-couple-pair" combinatorial synthetic schemes. Expression of random pairs of iPKS subunits from four BDL model systems in a yeast heterologous host created a diverse library of BDL congeners, including a polyketide with an unnatural skeleton and heat shock response-inducing activity. Pairwise heterocombinations of the iPKS subunits also helped to illuminate the innate, idiosyncratic programming of these enzymes. Even in combinatorial contexts, these biosynthetic programs remained largely unchanged, so that the iPKSs built their cognate biosynthons, coupled these building blocks into chimeric polyketide intermediates, and catalyzed intramolecular pairing to release macrocycles or α-pyrones. However, some heterocombinations also provoked stuttering, i.e., the relaxation of iPKSs chain length control to assemble larger homologous products. The success of such a plug and play approach to biosynthesize novel chemical diversity bodes well for bioprospecting unnatural polyketides for drug discovery.
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