Versatile polyketide biosynthesis platform for production of aromatic compounds in yeast

To accelerate the shift to bio-based production and overcome complicated functional implementation of natural and artificial biosynthetic pathways to industry relevant organisms, development of new, versatile, bio-based production platforms is required. Here we present a novel yeast platform for biosynthesis of bacterial aromatic polyketides. The platform is based on a synthetic polyketide synthase system enabling a first demonstration of bacterial aromatic polyketide biosynthesis in a eukaryotic host.

[1]  Keshav K. Nepal,et al.  Streptomycetes: Surrogate hosts for the genetic manipulation of biosynthetic gene clusters and production of natural products. , 2019, Biotechnology advances.

[2]  B. Møller,et al.  Heterologous production of the widely used natural food colorant carminic acid in Aspergillus nidulans , 2018, Scientific Reports.

[3]  D. Kallifidas,et al.  High-Yield Production of Herbicidal Thaxtomins and Thaxtomin Analogs in a Nonpathogenic Streptomyces Strain , 2018, Applied and Environmental Microbiology.

[4]  U. Mortensen,et al.  Synthesis of C‐Glucosylated Octaketide Anthraquinones in Nicotiana benthamiana by Using a Multispecies‐Based Biosynthetic Pathway , 2017, Chembiochem : a European journal of chemical biology.

[5]  Mathew M Jessop-Fabre,et al.  EasyClone‐MarkerFree: A vector toolkit for marker‐less integration of genes into Saccharomyces cerevisiae via CRISPR‐Cas9 , 2016, Biotechnology journal.

[6]  J. Keasling,et al.  Engineering Cellular Metabolism , 2016, Cell.

[7]  J. Keasling,et al.  CRISPR/Cas9 advances engineering of microbial cell factories. , 2016, Metabolic engineering.

[8]  Jay D Keasling,et al.  Multiplex metabolic pathway engineering using CRISPR/Cas9 in Saccharomyces cerevisiae. , 2015, Metabolic engineering.

[9]  Huimin Zhao,et al.  Recent advances in combinatorial biosynthesis for drug discovery , 2015, Drug design, development and therapy.

[10]  E. G. de Macedo Lemos,et al.  Biotechnology of polyketides: New breath of life for the novel antibiotic genetic pathways discovery through metagenomics , 2013, Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology].

[11]  S. Okamoto,et al.  Identification of the actinorhodin monomer and its related compound from a deletion mutant of the actVA-ORF4 gene of Streptomyces coelicolor A3(2). , 2012, Bioorganic & medicinal chemistry letters.

[12]  Enwu Liu,et al.  Identification of olivetolic acid cyclase from Cannabis sativa reveals a unique catalytic route to plant polyketides , 2012, Proceedings of the National Academy of Sciences.

[13]  Fuchao Xu,et al.  Type III polyketide synthases in natural product biosynthesis , 2012, IUBMB life.

[14]  David J Newman,et al.  Natural products as sources of new drugs over the 30 years from 1981 to 2010. , 2012, Journal of natural products.

[15]  C. Moody,et al.  Structural and biochemical characterization of ZhuI aromatase/cyclase from the R1128 polyketide pathway. , 2011, Biochemistry.

[16]  J. Keasling.  Manufacturing Molecules Through Metabolic Engineering , 2010, Science.

[17]  J. Medina-Franco,et al.  Nanaomycin A Selectively Inhibits DNMT3B and Reactivates Silenced Tumor Suppressor Genes in Human Cancer Cells , 2010, Molecular Cancer Therapeutics.

[18]  C. Khosla,et al.  Biosynthesis of aromatic polyketides in bacteria. , 2009, Accounts of chemical research.

[19]  Wenjun Zhang,et al.  Engineered biosynthesis of bacterial aromatic polyketides in Escherichia coli , 2008, Proceedings of the National Academy of Sciences.

[20]  R. Cox,et al.  Dissecting the component reactions catalyzed by the actinorhodin minimal polyketide synthase. , 2007, Biochemistry.

[21]  D. Newman,et al.  Natural products as sources of new drugs over the last 25 years. , 2007, Journal of natural products.

[22]  Andriy Luzhetskyy,et al.  Type II polyketide synthases: gaining a deeper insight into enzymatic teamwork. , 2007, Natural product reports.

[23]  I. Abe,et al.  Engineered biosynthesis of plant polyketides: chain length control in an octaketide-producing plant type III polyketide synthase. , 2005, Journal of the American Chemical Society.

[24]  M. Ozawa,et al.  Cloning, sequencing and heterologous expression of the medermycin biosynthetic gene cluster of Streptomyces sp. AM-7161: towards comparative analysis of the benzoisochromanequinone gene clusters. , 2003, Microbiology.

[25]  Ben Shen,et al.  Polyketide biosynthesis beyond the type I, II and III polyketide synthase paradigms. , 2003, Current opinion in chemical biology.

[26]  B. Shen,et al.  C-O Bond Formation by Polyketide Synthases , 2002, Science.

[27]  Blaine A. Pfeifer,et al.  Biosynthesis of Polyketides in Heterologous Hosts , 2001, Microbiology and Molecular Biology Reviews.

[28]  B. Moore,et al.  Engineering biodiversity with type II polyketide synthase genes , 2000, Antonie van Leeuwenhoek.

[29]  S. Ōmura,et al.  Heme-dependent radical generation: possible involvement in antimalarial action of non-peroxide microbial metabolites, nanaomycin A and radicicol. , 1999, Journal of antibiotics (Tokyo. 1968).

[30]  C. Hutchinson.  Combinatorial biosynthesis for new drug discovery. , 1998, Current opinion in microbiology.

[31]  L. Dijkhuizen,et al.  Production of actinorhodin-related "blue pigments" by Streptomyces coelicolor A3(2) , 1996, Journal of bacteriology.

[32]  J. Staunton,et al.  Polyketide biosynthesis: a millennium review. , 2001, Natural product reports.

[33]  C. Khosla,et al.  Engineered biosynthesis of novel polyketides. , 1993, Science.

[34]  D. Hopwood,et al.  Molecular cloning of the whole biosynthetic pathway of a Streptomyces antibiotic and its expression in a heterologous host , 1984, Nature.