Expression of biosynthetic gene clusters in heterologous hosts for natural product production and combinatorial biosynthesis
- 18 October 2006
- journal article
- Published by Taylor & Francis Ltd in Expert Opinion on Drug Discovery
- Vol. 1 (5), 409-437
- https://doi.org/10.1517/17460441.1.5.409
Abstract
Expression of biosynthetic gene clusters in heterologous hosts for natural product production and combinatorial biosynthesis is playing an increasingly important role in natural product-based drug discovery and development programmes. This review highlights the requirements and challenges associated with this conceptually simple strategy of using surrogate hosts for the production of natural products in good yields and for the generation of novel analogues by combinatorial biosynthesis methods, taking advantage of the recombinant DNA technologies and tools available in the model hosts. Specific topics addressed include: i) the mobilisation of biosynthetic gene clusters using different vector systems; ii) the selection of suitable model heterologous hosts; iii) the requirement of post-translational protein modifications and precursor supply within the model hosts; iv) the influence of promoters and pathway regulators; and v) the choice of suitable fermentation conditions. Lastly, the use of heterologous expression in combinatorial biosynthesis is addressed. Future directions for model heterologous host engineering and the optimisation of natural product biosynthetic gene cluster expression in heterologous hosts are also discussed.Keywords
This publication has 99 references indexed in Scilit:
- Genetic localization and heterologous expression of validamycin biosynthetic gene cluster isolated from Streptomyces hygroscopicus var. limoneus KCCM 11405 (IFO 12704)Gene, 2006
- Molecular Mechanisms Underlying Nonribosomal Peptide Synthesis: Approaches to New AntibioticsChemical Reviews, 2005
- Heterologous Biosynthesis of Truncated Hexaketides Derived from the Actinorhodin Polyketide SynthaseJournal of Natural Products, 2004
- Neocarzinostatin naphthoate synthase: an unique iterative type I PKS from neocarzinostatin producer Streptomyces carzinostaticusFEBS Letters, 2004
- Accessing Natural Products by Combinatorial BiosynthesisScience's STKE, 2004
- Natural Products as Sources of New Drugs over the Period 1981−2002Journal of Natural Products, 2003
- Cloning and engineering of the cinnamycin biosynthetic gene cluster from Streptomyces cinnamoneus cinnamoneus DSM 40005Proceedings of the National Academy of Sciences of the United States of America, 2003
- Artificial chromosome libraries ofStreptomyces coelicolorA3(2) andPlanobispora roseaFEMS Microbiology Letters, 2003
- The entire nogalamycin biosynthetic gene cluster of Streptomyces nogalater: characterization of a 20-kb DNA region and generation of hybrid structuresMolecular Genetics and Genomics, 2001
- Molecular cloning of the whole biosynthetic pathway of a Streptomyces antibiotic and its expression in a heterologous hostNature, 1984