Microbial Soluble Aromatic Prenyltransferases for Engineered Biosynthesis

Overview

Journal Synth Syst Biotechnol

Specialty Biotechnology

Date 2021 Mar 29

PMID 33778178

Citations 5

Authors

He-Ping Chen

Ikuro Abe

Affiliations

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Abstract

Prenyltransferase (PTase) enzymes play crucial roles in natural product biosynthesis by transferring isoprene unit(s) to target substrates, thereby generating prenylated compounds. The prenylation step leads to a diverse group of natural products with improved membrane affinity and enhanced bioactivity, as compared to the non-prenylated forms. The last two decades have witnessed increasing studies on the identification, characterization, enzyme engineering, and synthetic biology of microbial PTase family enzymes. We herein summarize several examples of microbial soluble aromatic PTases for chemoenzymatic syntheses of unnatural novel prenylated compounds.

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References

Gu W, Dong S, Sarkar S, Nair S, Schmidt E . The Biochemistry and Structural Biology of Cyanobactin Pathways: Enabling Combinatorial Biosynthesis. Methods Enzymol. 2018; 604:113-163. PMC: 6463883. DOI: 10.1016/bs.mie.2018.03.002. View

Newmister S, Li S, Garcia-Borras M, Sanders J, Yang S, Lowell A . Structural basis of the Cope rearrangement and cyclization in hapalindole biogenesis. Nat Chem Biol. 2018; 14(4):345-351. PMC: 5880276. DOI: 10.1038/s41589-018-0003-x. View

Tanner M . Mechanistic studies on the indole prenyltransferases. Nat Prod Rep. 2014; 32(1):88-101. DOI: 10.1039/c4np00099d. View

Luk L, Qian Q, Tanner M . A cope rearrangement in the reaction catalyzed by dimethylallyltryptophan synthase?. J Am Chem Soc. 2011; 133(32):12342-5. DOI: 10.1021/ja2034969. View

Metzger U, Schall C, Zocher G, Unsold I, Stec E, Li S . The structure of dimethylallyl tryptophan synthase reveals a common architecture of aromatic prenyltransferases in fungi and bacteria. Proc Natl Acad Sci U S A. 2009; 106(34):14309-14. PMC: 2732893. DOI: 10.1073/pnas.0904897106. View

Li W . Bringing Bioactive Compounds into Membranes: The UbiA Superfamily of Intramembrane Aromatic Prenyltransferases. Trends Biochem Sci. 2016; 41(4):356-370. PMC: 4911241. DOI: 10.1016/j.tibs.2016.01.007. View

Hillwig M, Zhu Q, Ittiamornkul K, Liu X . Discovery of a Promiscuous Non-Heme Iron Halogenase in Ambiguine Alkaloid Biogenesis: Implication for an Evolvable Enzyme Family for Late-Stage Halogenation of Aliphatic Carbons in Small Molecules. Angew Chem Int Ed Engl. 2016; 55(19):5780-4. DOI: 10.1002/anie.201601447. View

Estrada P, Morita M, Hao Y, Schmidt E, Nair S . A Single Amino Acid Switch Alters the Isoprene Donor Specificity in Ribosomally Synthesized and Post-Translationally Modified Peptide Prenyltransferases. J Am Chem Soc. 2018; 140(26):8124-8127. PMC: 6467259. DOI: 10.1021/jacs.8b05187. View

Awakawa T, Zhang L, Wakimoto T, Hoshino S, Mori T, Ito T . A methyltransferase initiates terpene cyclization in teleocidin B biosynthesis. J Am Chem Soc. 2014; 136(28):9910-3. DOI: 10.1021/ja505224r. View

10.

He H, Bian G, Herbst-Gervasoni C, Mori T, Shinsky S, Hou A . Discovery of the cryptic function of terpene cyclases as aromatic prenyltransferases. Nat Commun. 2020; 11(1):3958. PMC: 7414894. DOI: 10.1038/s41467-020-17642-2. View

11.

Brunson J, McKinnie S, Chekan J, McCrow J, Miles Z, Bertrand E . Biosynthesis of the neurotoxin domoic acid in a bloom-forming diatom. Science. 2018; 361(6409):1356-1358. PMC: 6276376. DOI: 10.1126/science.aau0382. View

12.

Charron G, Tsou L, Maguire W, Yount J, Hang H . Alkynyl-farnesol reporters for detection of protein S-prenylation in cells. Mol Biosyst. 2010; 7(1):67-73. PMC: 4231476. DOI: 10.1039/c0mb00183j. View

13.

Abe I, Tanaka H, Abe T, Noguchi H . Enzymatic formation of unnatural cytokinin analogs by adenylate isopentenyltransferase from mulberry. Biochem Biophys Res Commun. 2007; 355(3):795-800. DOI: 10.1016/j.bbrc.2007.02.032. View

14.

Mori T, Zhang L, Awakawa T, Hoshino S, Okada M, Morita H . Manipulation of prenylation reactions by structure-based engineering of bacterial indolactam prenyltransferases. Nat Commun. 2016; 7:10849. PMC: 4786772. DOI: 10.1038/ncomms10849. View

15.

Hao Y, Pierce E, Roe D, Morita M, McIntosh J, Agarwal V . Molecular basis for the broad substrate selectivity of a peptide prenyltransferase. Proc Natl Acad Sci U S A. 2016; 113(49):14037-14042. PMC: 5150373. DOI: 10.1073/pnas.1609869113. View

16.

Murray L, McKinnie S, Pepper H, Erni R, Miles Z, Cruickshank M . Total Synthesis Establishes the Biosynthetic Pathway to the Naphterpin and Marinone Natural Products. Angew Chem Int Ed Engl. 2018; 57(34):11009-11014. PMC: 6248334. DOI: 10.1002/anie.201804351. View

17.

Winkelblech J, Fan A, Li S . Prenyltransferases as key enzymes in primary and secondary metabolism. Appl Microbiol Biotechnol. 2015; 99(18):7379-97. DOI: 10.1007/s00253-015-6811-y. View

18.

Mitchell A, Zhu Q, Maggiolo A, Ananth N, Hillwig M, Liu X . Structural basis for halogenation by iron- and 2-oxo-glutarate-dependent enzyme WelO5. Nat Chem Biol. 2016; 12(8):636-40. PMC: 5391150. DOI: 10.1038/nchembio.2112. View

19.

Donia M, Schmidt E . Linking chemistry and genetics in the growing cyanobactin natural products family. Chem Biol. 2011; 18(4):508-19. PMC: 3119926. DOI: 10.1016/j.chembiol.2011.01.019. View

20.

Zheng L, Mai P, Fan A, Li S . Switching a regular tryptophan C4-prenyltransferase to a reverse tryptophan-containing cyclic dipeptide C3-prenyltransferase by sequential site-directed mutagenesis. Org Biomol Chem. 2018; 16(36):6688-6694. DOI: 10.1039/c8ob01735b. View