Coordinating precursor supply for pharmaceutical polyketide production in Streptomyces. (June 2021)

• Record Type: Journal Article
• Authors: Li, Shanshan; Li, Zilong; Pang, Shen; Xiang, Wensheng; Wang, Weishan
• Is Part Of: Current opinion in biotechnology. Volume 69(2021)
• Page Start: 26
• Page End: 34
• Publication Date: 2021-06
• Subjects: Biotechnology -- Periodicals; 660.6
• DOI: 10.1016/j.copbio.2020.11.006
• Languages: English
• ISSNs: 0958-1669

Abstract

Graphical abstract: Highlights: Polyketide precursor pathways are key biological entities for synthetic biology driven strain improvement. Diverse native and heterologous precursor pathways for polyketide biosynthesis are available. Bottlenecks restricting carbon flux towards polyketides can be addressed systematically. Coordination of precursor supply can facilitate pharmaceutical polyketide production. Abstract : The widely used polyketide pharmaceuticals in medicine and agriculture are mainly produced by Streptomyces species. These compounds, as secondary metabolites, are not involved in essential cellular processes and are usually produced during the stationary phase of fermentation. Consequently, their yields and productivities are often low and frequently limited by the availability of the precursors. The precursor pathways, therefore, are key entities for synthetic biology-driven design and optimization. We discuss recent advances in precursor engineering, in both Streptomyces and other bacteria, focusing on the diverse native and heterologous precursor pathways that could be rewired for polyketide titer improvement. We also highlight the coordination of other required factors to direct the precursors towards polyketide biosynthesis. The precursor-supply enhancement tools and strategies covered in this review will facilitate the design and construction of synthetic Streptomyces 'cell-factories' for efficient polyketide production.