Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Oct 14:10:1017190.
doi: 10.3389/fbioe.2022.1017190. eCollection 2022.

Engineered biosynthesis of plant polyketides by type III polyketide synthases in microorganisms

Chang Liu  1 , Sijin Li  1
Affiliations
Review

Engineered biosynthesis of plant polyketides by type III polyketide synthases in microorganisms

Chang Liu et al. Front Bioeng Biotechnol. .

Erratum in

Abstract

Plant specialized metabolites occupy unique therapeutic niches in human medicine. A large family of plant specialized metabolites, namely plant polyketides, exhibit diverse and remarkable pharmaceutical properties and thereby great biomanufacturing potential. A growing body of studies has focused on plant polyketide synthesis using plant type III polyketide synthases (PKSs), such as flavonoids, stilbenes, benzalacetones, curcuminoids, chromones, acridones, xanthones, and pyrones. Microbial expression of plant type III PKSs and related biosynthetic pathways in workhorse microorganisms, such as Saccharomyces cerevisiae, Escherichia coli, and Yarrowia lipolytica, have led to the complete biosynthesis of multiple plant polyketides, such as flavonoids and stilbenes, from simple carbohydrates using different metabolic engineering approaches. Additionally, advanced biosynthesis techniques led to the biosynthesis of novel and complex plant polyketides synthesized by diversified type III PKSs. This review will summarize efforts in the past 10 years in type III PKS-catalyzed natural product biosynthesis in microorganisms, especially the complete biosynthesis strategies and achievements.

Keywords: biosynthesis achievements; biosynthesis strategies; complete biosynthesis; microorganisms; plant polyketides; type III polyketide synthases.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Reconstructed biosynthetic pathway for most explored type III PKS-derived polyketides (e.g., pinocembrin, pinosylvin, naringenin, and resveratrol) in microbial hosts. Dotted arrows refer to multiple steps. Genes and enzymes in green circle are heterologous genes from plants or bacterium. G6P, glucose-6-phosphate; PEP, phosphoenolpyruvate; E4P, erythrose-4-phosphate; DAHP, 3-deoxy-D-arabino-2-heptulosonic acid 7-phosphate; L-Phe, L-phenylalanine; L-Tyr, L-tyrosine; PAL, phenylalanine ammonia lyase; TAL, tyrosine ammonia lyase; C4H, cinnamic acid hydroxylase; CPR, P450 reductase; 4CL, 4-coumaroyl-coA ligase; CHS, chalcone synthase; CHI, chalcone isomerase; STS, stilbene synthase.
FIGURE 2
FIGURE 2
An overview of precursor enhancement engineering in E. coli. Genes and enzymes in red are overexpressed. Genes and enzymes in blue are deleted or downregulated. Genes and enzymes in green are heterologous expressed. Dotted arrows refer to multiple steps. G6P, glucose-6-phosphate; PEP, phosphoenolpyruvate; E4P, erythrose-4-phosphate; DAHP, 3-deoxy-D-arabino-2-heptulosonic acid 7-phosphate; fabH, gene that encodes 3-oxoacyl carrier protein synthase III; fabB/fabF, genes that encode the beta-ketoacyl-acp synthase I/II protein; MatB, malonylCoA synthetase; MatC, malonate carrier protein; ACS, acetyl-CoA synthase; ACC, acetyl-CoA carboxylase; TCA cycle, tricarboxylic acid cycle; ppsA, phosphoenolpyruvate synthase; tktA, transketolase; tyrAfbr, chorismate mutase-prephenate dehydrogenase feedback inhibition resistant variant; aroGfbr, DAHP synthase feedback inhibition resistant variant; TyrR, a DNA binding transcriptional regulatory protein.
FIGURE 3
FIGURE 3
An overview of precursor enhancement engineering in S. cerevisiae. Genes and enzymes in red are overexpressed. Genes and enzymes in blue are deleted. Dotted arrows refer to multiple steps. G6P, glucose-6-phosphate; PEP, phosphoenolpyruvate; E4P, erythrose-4-phosphate; DAHP, 3-deoxy-D-arabino-2-heptulosonic acid 7-phosphate; ARO4K229L, DAHP synthase feedback inhibition resistant variants; ARO7G141S, chorismate mutase feedback inhibition resistant variants; PAD1, phenyl acrylic acid decarboxylase; PDC5, pyruvate decarboxylase; ARO10, phenylpyruvate decarboxylase; ACS, acetyl-CoA synthase; ACC, acetyl-CoA carboxylase.
FIGURE 4
FIGURE 4
Synthesis of plant polyketides from malonyl-CoA and CoA starters. CHS, chalcone synthase; CHI, chalcone isomerase; STS, stilbene synthase; CUS, curcuminoid synthase; CURS, curcumin synthase; DCS, diketide-CoA synthase; SPS, styrylpyrone synthase; KOMT, kava O-methyltransferase; QNS, quinolone synthase; 2-PS, 2-pyrone synthase; BAS, benzalacetone synthase; BAR, benzalacetone reductase.
See this image and copyright information in PMC

References

    1. Abdel-Mawgoud A. M., Markham K. A., Palmer C. M., Liu N., Stephanopoulos G., Alper H. S. (2018). Metabolic engineering in the host Yarrowia lipolytica . Metab. Eng. 50, 192–208. 10.1016/j.ymben.2018.07.016 - DOI - PubMed
    1. Aggarwal B. B., Sung B. (2009). Pharmacological basis for the role of curcumin in chronic diseases: an age-old spice with modern targets. Trends Pharmacol. Sci. 30, 85–94. 10.1016/j.tips.2008.11.002 - DOI - PubMed
    1. Ahmad B., Rehman M. U., Amin I., Arif A., Rasool S., Bhat S. A., et al. (2015). A review on pharmacological properties of zingerone (4-(4-hydroxy-3-methoxyphenyl)-2-butanone). Sci. World J. 2015, 1–6. 10.1155/2015/816364 - DOI - PMC - PubMed
    1. Apel A. R., D’Espaux L., Wehrs M., Sachs D., Li R. A., Tong G. J., et al. (2017). A Cas9-based toolkit to program gene expression in Saccharomyces cerevisiae . Nucleic Acids Res. 45, 496–508. 10.1093/nar/gkw1023 - DOI - PMC - PubMed
    1. Austin M., Bowman M., Ferrer J., Schroder J., Noel J. (2004). An aldol switch discovered in stilbene synthases mediates cyclization specificity of type III polyketide synthases. Chem. Biol. 11, 1179–1194. 10.1016/j.chembiol.2004.05.024 - DOI - PubMed

LinkOut - more resources