In Vitro Biosynthesis of Unnatural Enterocin and Wailupemycin Polyketides

Overview

Journal J Nat Prod

Date 2009 Feb 14

PMID 19215142

Citations 16

Authors

John A Kalaitzis

Qian Cheng

Paul M Thomas

Neil L Kelleher

Bradley S Moore

Affiliations

Soon will be listed here.

Abstract

Nature has evolved finely tuned strategies to synthesize rare and complex natural products such as the enterocin family of polyketides from the marine bacterium Streptomyces maritimus. Herein we report the directed ex vivo multienzyme syntheses of 24 unnatural 5-deoxyenterocin and wailupemycin F and G analogues, 18 of which are new. We have generated molecular diversity by priming the enterocin biosynthesis enzymes with unnatural substrates and have illustrated further the uniqueness of this type II polyketide synthase by way of exploiting its unusual starter unit biosynthesis pathways.

Citing Articles

Advanced Technologies for Large Scale Supply of Marine Drugs.

Martinez H, Santos M, Pedraza L, Testera A Mar Drugs. 2025; 23(2).

PMID: 39997193 PMC: 11857447. DOI: 10.3390/md23020069.

Expanding the Chemical Diversity of Secondary Metabolites Produced by Two Marine-Derived Enterocin- and Wailupemycin-Producing Strains.

Xia K, Shang J, Sun J, Zhu W, Fu P ACS Omega. 2023; 8(31):28886-28897.

PMID: 37576654 PMC: 10413459. DOI: 10.1021/acsomega.3c04199.

Biosynthesis of rumbrins and inspiration for discovery of HIV inhibitors.

Zhong B, Wan J, Shang C, Wen J, Wang Y, Bai J Acta Pharm Sin B. 2022; 12(11):4193-4203.

PMID: 36386473 PMC: 9643285. DOI: 10.1016/j.apsb.2022.02.005.

Three Rings to Rule Them All: How Versatile Flavoenzymes Orchestrate the Structural Diversification of Natural Products.

Toplak M, Teufel R Biochemistry. 2021; 61(2):47-56.

PMID: 34962769 PMC: 8772269. DOI: 10.1021/acs.biochem.1c00763.

High-yield 'one-pot' biosynthesis of raspberry ketone, a high-value fine chemical.

Moore S, Tosi T, Bell D, Hleba Y, Polizzi K, Freemont P Synth Biol (Oxf). 2021; 6(1):ysab021.

PMID: 34712844 PMC: 8546603. DOI: 10.1093/synbio/ysab021.

References

Sattely E, Fischbach M, Walsh C . Total biosynthesis: in vitro reconstitution of polyketide and nonribosomal peptide pathways. Nat Prod Rep. 2008; 25(4):757-93. DOI: 10.1039/b801747f. View

Xiang L, Kalaitzis J, Nilsen G, Chen L, Moore B . Mutational analysis of the enterocin favorskii biosynthetic rearrangement. Org Lett. 2002; 4(6):957-60. DOI: 10.1021/ol0255155. View

Xiang L, Moore B . Characterization of benzoyl coenzyme A biosynthesis genes in the enterocin-producing bacterium "Streptomyces maritimus". J Bacteriol. 2003; 185(2):399-404. PMC: 145315. DOI: 10.1128/JB.185.2.399-404.2003. View

Izumikawa M, Cheng Q, Moore B . Priming type II polyketide synthases via a type II nonribosomal peptide synthetase mechanism. J Am Chem Soc. 2006; 128(5):1428-9. PMC: 2531066. DOI: 10.1021/ja0559707. View

Dorrestein P, Kelleher N . Dissecting non-ribosomal and polyketide biosynthetic machineries using electrospray ionization Fourier-Transform mass spectrometry. Nat Prod Rep. 2006; 23(6):893-918. DOI: 10.1039/b511400b. View

Bumpus S, Kelleher N . Accessing natural product biosynthetic processes by mass spectrometry. Curr Opin Chem Biol. 2008; 12(5):475-82. PMC: 2642909. DOI: 10.1016/j.cbpa.2008.07.022. View

Fecik R . Natural product biosynthesis moves in vitro. Nat Chem Biol. 2007; 3(9):531-2. DOI: 10.1038/nchembio0907-531. View

Cheng Q, Xiang L, Izumikawa M, Meluzzi D, Moore B . Enzymatic total synthesis of enterocin polyketides. Nat Chem Biol. 2007; 3(9):557-8. DOI: 10.1038/nchembio.2007.22. View

Piel J, Hertweck C, Shipley P, Hunt D, NEWMAN M, Moore B . Cloning, sequencing and analysis of the enterocin biosynthesis gene cluster from the marine isolate 'Streptomyces maritimus': evidence for the derailment of an aromatic polyketide synthase. Chem Biol. 2001; 7(12):943-55. DOI: 10.1016/s1074-5521(00)00044-2. View

10.

Kopp F, Marahiel M . Where chemistry meets biology: the chemoenzymatic synthesis of nonribosomal peptides and polyketides. Curr Opin Biotechnol. 2007; 18(6):513-20. DOI: 10.1016/j.copbio.2007.09.009. View

11.

Xiang L, Moore B . Inactivation, complementation, and heterologous expression of encP, a novel bacterial phenylalanine ammonia-lyase gene. J Biol Chem. 2002; 277(36):32505-9. DOI: 10.1074/jbc.M204171200. View

12.

Roessner C, Scott A . Achieving natural product synthesis and diversity via catalytic networking ex vivo. Chem Biol. 1996; 3(5):325-30. DOI: 10.1016/s1074-5521(96)90114-3. View

13.

Xiang L, Kalaitzis J, Moore B . EncM, a versatile enterocin biosynthetic enzyme involved in Favorskii oxidative rearrangement, aldol condensation, and heterocycle-forming reactions. Proc Natl Acad Sci U S A. 2004; 101(44):15609-14. PMC: 524846. DOI: 10.1073/pnas.0405508101. View

14.

Hertweck C, Xiang L, Kalaitzis J, Cheng Q, Palzer M, Moore B . Context-dependent behavior of the enterocin iterative polyketide synthase; a new model for ketoreduction. Chem Biol. 2004; 11(4):461-8. DOI: 10.1016/j.chembiol.2004.03.018. View

15.

Kalaitzis J, Izumikawa M, Xiang L, Hertweck C, Moore B . Mutasynthesis of enterocin and wailupemycin analogues. J Am Chem Soc. 2003; 125(31):9290-1. DOI: 10.1021/ja035973o. View