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Fungal Genet Biol. 2016 Apr;89:52-61. doi: 10.1016/j.fgb.2016.01.005. Epub 2016 Feb 2.

Saccharomyces cerevisiae as a tool for mining, studying and engineering fungal polyketide synthases.

Author information

1
Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, CA 90095, United States.
2
Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, CA 90095, United States; Department of Chemistry and Biochemistry, University of California, Los Angeles, CA 90095, United States. Electronic address: yitang@ucla.edu.
3
Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, CA 90095, United States; Engineering Research Center of Industrial Microbiology (Ministry of Education), College of Life Sciences, Fujian Normal University, Fuzhou, Fujian 350108, China; State Key Laboratory of Microbial Metabolism, Shanghai Jiao Tong University, Shanghai 200030, China.

Abstract

Small molecule secondary metabolites produced by organisms such as plants, bacteria, and fungi form a fascinating and important group of natural products, many of which have shown promise as medicines. Fungi in particular have been important sources of natural product polyketide pharmaceuticals. While the structural complexity of these polyketides makes them interesting and useful bioactive compounds, these same features also make them difficult and expensive to prepare and scale-up using synthetic methods. Currently, nearly all commercial polyketides are prepared through fermentation or semi-synthesis. However, elucidation and engineering of polyketide pathways in the native filamentous fungi hosts are often hampered due to a lack of established genetic tools and of understanding of the regulation of fungal secondary metabolisms. Saccharomyces cerevisiae has many advantages beneficial to the study and development of polyketide pathways from filamentous fungi due to its extensive genetic toolbox and well-studied metabolism. This review highlights the benefits S. cerevisiae provides as a tool for mining, studying, and engineering fungal polyketide synthases (PKSs), as well as notable insights this versatile tool has given us into the mechanisms and products of fungal PKSs.

KEYWORDS:

Heterologous host; Megasynthases; Polyketides

PMID:
26850128
PMCID:
PMC4789138
DOI:
10.1016/j.fgb.2016.01.005
[Indexed for MEDLINE]
Free PMC Article

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