ReviewDrug design, development and therapy2015
Recent advances in combinatorial biosynthesis for drug discovery.
Review in Drug design, development and therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed.
- Creation of bioactive non-natural flavonoids via combinatorial prenylation-glycosylation cascades.mLife · 2026Article
- Advances in microbial biosynthesis of indirubin.Chinese herbal medicines · 2026Review
- Excavation of acoustic nanostructures biosynthesis gene clusters by combinatorial strategy.Advanced biotechnology · 2025Article
- Advanced Technologies for Large Scale Supply of Marine Drugs.Marine drugs · 2025Review
- Engineering a promiscuous prenyltransferase for selective biosynthesis of an undescribed bioactive cannabinoid analog.Communications biology · 2025Article
- Functional Diversity and Engineering of the Adenylation Domains in Nonribosomal Peptide Synthetases.Marine drugs · 2024Review
- Biotransformation-coupled mutasynthesis for the generation of novel pristinamycin derivatives by engineering the phenylglycine residue.RSC chemical biology · 2023Article
- Engineering Siderophore Biosynthesis and Regulation Pathways to Increase Diversity and Availability.Biomolecules · 2023Review
- Analogues of Anticancer Natural Products: Chiral Aspects.International journal of molecular sciences · 2023Review
- Production of tailored hydroxylated prodiginine showing combinatorial activity with rhamnolipids against plant-parasitic nematodes.Frontiers in microbiology · 2023Article
- Thiophenes-Naturally Occurring Plant Metabolites: Biological Activities and In Silico Evaluation of Their Potential as Cathepsin D Inhibitors.Plants (Basel, Switzerland) · 2022Review
- Directed Biosynthesis of New to Nature Alkaloids in a HeterologousFrontiers in plant science · 2022Article
- Advances in Biosynthesis of Natural Products from Marine Microorganisms.Microorganisms · 2021Review
- Extensive expansion of the chemical diversity of fusidane-type antibiotics using a stochastic combinational strategy.Acta pharmaceutica Sinica. B · 2021Article
- CRISPR/Cas9-Mediated Genome Editing in Comfrey (Molecules (Basel, Switzerland) · 2021Article
- cblaster: a remote search tool for rapid identification and visualization of homologous gene clusters.Bioinformatics advances · 2021Article
- Programmable polyketide biosynthesis platform for production of aromatic compounds in yeast.Synthetic and systems biotechnology · 2020Article
- Combinatorial Enzymatic Synthesis of Unnatural Long-Chain β-Branch Pyrones by a Highly Promiscuous Enzyme.ACS omega · 2019Article
- Antitussive and Anti-inflammatory Dual-active Agents Developed from Natural Product Lead Compound 1-Methylhydantoin.Molecules (Basel, Switzerland) · 2019Article
- Active site labeling of fatty acid and polyketide acyl-carrier protein transacylases.Organic & biomolecular chemistry · 2019Article
Corrections and comments
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Because of extraordinary structural diversity and broad biological activities, natural products have played a significant role in drug discovery. These therapeutically important secondary metabolites are assembled and modified by dedicated biosynthetic pathways in their host living organisms. Traditionally, chemists have attempted to synthesize natural product analogs that are important sources of new drugs. However, the extraordinary structural complexity of natural products sometimes makes it challenging for traditional chemical synthesis, which usually involves multiple steps, harsh conditions, toxic organic solvents, and byproduct wastes. In contrast, combinatorial biosynthesis exploits substrate promiscuity and employs engineered enzymes and pathways to produce novel "unnatural" natural products, substantially expanding the structural diversity of natural products with potential pharmaceutical value. Thus, combinatorial biosynthesis provides an environmentally friendly way to produce natural product analogs. Efficient expression of the combinatorial biosynthetic pathway in genetically tractable heterologous hosts can increase the titer of the compound, eventually resulting in less expensive drugs. In this review, we will discuss three major strategies for combinatorial biosynthesis: 1) precursor-directed biosynthesis; 2) enzyme-level modification, which includes swapping of the entire domains, modules and subunits, site-specific mutagenesis, and directed evolution; 3) pathway-level recombination. Recent examples of combinatorial biosynthesis employing these strategies will also be highlighted in this review.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.