Exploiting the Biosynthetic Potential of Type III Polyketide Synthases

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2016 Jun 25

PMID 27338328

Citations 25

Authors

Yan Ping Lim

Maybelle K Go

Wen Shan Yew

Affiliations

Soon will be listed here.

Abstract

Polyketides are structurally and functionally diverse secondary metabolites that are biosynthesized by polyketide synthases (PKSs) using acyl-CoA precursors. Recent studies in the engineering and structural characterization of PKSs have facilitated the use of target enzymes as biocatalysts to produce novel functionally optimized polyketides. These compounds may serve as potential drug leads. This review summarizes the insights gained from research on type III PKSs, from the discovery of chalcone synthase in plants to novel PKSs in bacteria and fungi. To date, at least 15 families of type III PKSs have been characterized, highlighting the utility of PKSs in the development of natural product libraries for therapeutic development.

Citing Articles

Designing a highly efficient type III polyketide whole-cell catalyst with minimized byproduct formation.

Xiang L, Zhang X, Lei Y, Wu J, Yan G, Chen W Biotechnol Biofuels Bioprod. 2024; 17(1):93.

PMID: 38961423 PMC: 11223281. DOI: 10.1186/s13068-024-02545-x.

Characterization of Genomic, Physiological, and Probiotic Features of JS21 Strain Isolated from Traditional Fermented Jiangshui.

Liu Y, Wang S, Wang L, Lu H, Zhang T, Zeng W Foods. 2024; 13(7).

PMID: 38611386 PMC: 11011416. DOI: 10.3390/foods13071082.

A hybrid pathway for self-sustained luminescence.

Palkina K, Karataeva T, Perfilov M, Fakhranurova L, Markina N, Somermeyer L Sci Adv. 2024; 10(10):eadk1992.

PMID: 38457503 PMC: 10923510. DOI: 10.1126/sciadv.adk1992.

Characteristic of the gene candidate SecARS encoding alkylresorcinol synthase in Secale.

Targonska-Karasek M, Kwiatek M, Groszyk J, Walczewski J, Kowalczyk M, Pawelec S Mol Biol Rep. 2023; 50(10):8373-8383.

PMID: 37615923 PMC: 10520190. DOI: 10.1007/s11033-023-08684-y.

QT-GWAS: A novel method for unveiling biosynthetic loci affecting qualitative metabolic traits.

Brouckaert M, Peng M, Hofer R, El Houari I, Darrah C, Storme V Mol Plant. 2023; 16(7):1212-1227.

PMID: 37349988 PMC: 7614782. DOI: 10.1016/j.molp.2023.06.004.

References

Bangera M, Thomashow L . Identification and characterization of a gene cluster for synthesis of the polyketide antibiotic 2,4-diacetylphloroglucinol from Pseudomonas fluorescens Q2-87. J Bacteriol. 1999; 181(10):3155-63. PMC: 93771. DOI: 10.1128/JB.181.10.3155-3163.1999. View

Ferrer J, Jez J, Bowman M, Dixon R, Noel J . Structure of chalcone synthase and the molecular basis of plant polyketide biosynthesis. Nat Struct Biol. 1999; 6(8):775-84. DOI: 10.1038/11553. View

Akiyama T, Shibuya M, Liu H, Ebizuka Y . p-Coumaroyltriacetic acid synthase, a new homologue of chalcone synthase, from Hydrangea macrophylla var. thunbergii. Eur J Biochem. 1999; 263(3):834-9. DOI: 10.1046/j.1432-1327.1999.00562.x. View

Funa N, Ohnishi Y, Fujii I, Shibuya M, Ebizuka Y, Horinouchi S . A new pathway for polyketide synthesis in microorganisms. Nature. 1999; 400(6747):897-9. DOI: 10.1038/23748. View

Yamaguchi T, Kurosaki F, Suh D, Sankawa U, Nishioka M, Akiyama T . Cross-reaction of chalcone synthase and stilbene synthase overexpressed in Escherichia coli. FEBS Lett. 1999; 460(3):457-61. DOI: 10.1016/s0014-5793(99)01403-9. View

Jez J, Ferrer J, Bowman M, Dixon R, Noel J . Dissection of malonyl-coenzyme A decarboxylation from polyketide formation in the reaction mechanism of a plant polyketide synthase. Biochemistry. 2000; 39(5):890-902. DOI: 10.1021/bi991489f. View

Springob K, Lukacin R, Ernwein C, Groning I, Matern U . Specificities of functionally expressed chalcone and acridone synthases from Ruta graveolens. Eur J Biochem. 2000; 267(22):6552-9. DOI: 10.1046/j.1432-1327.2000.01746.x. View

Jez J, Austin M, Ferrer J, Bowman M, Schroder J, Noel J . Structural control of polyketide formation in plant-specific polyketide synthases. Chem Biol. 2001; 7(12):919-30. DOI: 10.1016/s1074-5521(00)00041-7. View

Abe I, Takahashi Y, Morita H, Noguchi H . Benzalacetone synthase. A novel polyketide synthase that plays a crucial role in the biosynthesis of phenylbutanones in Rheum palmatum. Eur J Biochem. 2001; 268(11):3354-9. DOI: 10.1046/j.1432-1327.2001.02255.x. View

10.

Morita H, Noguchi H, Schroder J, Abe I . Novel polyketides synthesized with a higher plant stilbene synthase. Eur J Biochem. 2001; 268(13):3759-66. DOI: 10.1046/j.1432-1327.2001.02289.x. View

11.

Pfeifer V, Nicholson G, Ries J, Recktenwald J, Schefer A, Shawky R . A polyketide synthase in glycopeptide biosynthesis: the biosynthesis of the non-proteinogenic amino acid (S)-3,5-dihydroxyphenylglycine. J Biol Chem. 2001; 276(42):38370-7. DOI: 10.1074/jbc.M106580200. View

12.

Staunton J, Weissman K . Polyketide biosynthesis: a millennium review. Nat Prod Rep. 2001; 18(4):380-416. DOI: 10.1039/a909079g. View

13.

Funa N, Ohnishi Y, Ebizuka Y, Horinouchi S . Properties and substrate specificity of RppA, a chalcone synthase-related polyketide synthase in Streptomyces griseus. J Biol Chem. 2001; 277(7):4628-35. DOI: 10.1074/jbc.M110357200. View

14.

Lukacin R, Schreiner S, Matern U . Transformation of acridone synthase to chalcone synthase. FEBS Lett. 2001; 508(3):413-7. DOI: 10.1016/s0014-5793(01)03061-7. View

15.

Jez J, Bowman M, Noel J . Expanding the biosynthetic repertoire of plant type III polyketide synthases by altering starter molecule specificity. Proc Natl Acad Sci U S A. 2002; 99(8):5319-24. PMC: 122767. DOI: 10.1073/pnas.082590499. View

16.

Funa N, Ohnishi Y, Ebizuka Y, Horinouchi S . Alteration of reaction and substrate specificity of a bacterial type III polyketide synthase by site-directed mutagenesis. Biochem J. 2002; 367(Pt 3):781-9. PMC: 1222926. DOI: 10.1042/BJ20020953. View

17.

Samappito S, Page J, Schmidt J, De-Eknamkul W, Kutchan T . Molecular characterization of root-specific chalcone synthases from Cassia alata. Planta. 2002; 216(1):64-71. DOI: 10.1007/s00425-002-0872-8. View

18.

Eckermann C, Schroder G, Eckermann S, Strack D, Schmidt J, Schneider B . Stilbenecarboxylate biosynthesis: a new function in the family of chalcone synthase-related proteins. Phytochemistry. 2003; 62(3):271-86. DOI: 10.1016/s0031-9422(02)00554-x. View

19.

Austin M, Noel J . The chalcone synthase superfamily of type III polyketide synthases. Nat Prod Rep. 2003; 20(1):79-110. DOI: 10.1039/b100917f. View

20.

Abe I, Takahashi Y, Lou W, Noguchi H . Enzymatic formation of unnatural novel polyketides from alternate starter and nonphysiological extension substrate by chalcone synthase. Org Lett. 2003; 5(8):1277-80. DOI: 10.1021/ol0300165. View