Heterologous Expression and Manipulation of Three Tetracycline Biosynthetic Pathways

Overview

Journal Angew Chem Int Ed Engl

Specialty Chemistry

Date 2012 Oct 2

PMID 23024027

Citations 18

Authors

Peng Wang

Woncheol Kim

Lauren B Pickens

Xue Gao

Yi Tang

Affiliations

Soon will be listed here.

Abstract

A very accommodating host: Three tetracycline biosynthetic pathways were overexpressed and manipulated in the heterologous host Streptomyces lividans K4-114. Through the inactivation of various genes and characterization of the resulting biosynthetic intermediates, new tetracycline-modifying enzymes were identified (see scheme).

Citing Articles

ActVI-ORFA directs metabolic flux towards actinorhodin by preventing intermediate degradation.

Zhu X, Wang R, Siitonen V, Vuksanovic N, Silvaggi N, Melancon Iii C PLoS One. 2024; 19(8):e0308684.

PMID: 39121077 PMC: 11315284. DOI: 10.1371/journal.pone.0308684.

Resistance and phylogeny guided discovery reveals structural novelty of tetracycline antibiotics.

Li L, Hu Y, Sun J, Yu L, Shi J, Wang Z Chem Sci. 2022; 13(43):12892-12898.

PMID: 36519048 PMC: 9645399. DOI: 10.1039/d2sc03965f.

Crystal structure determination of the halogenase CtcP from Streptomyces aureofaciens.

Yin L Acta Crystallogr F Struct Biol Commun. 2022; 78(Pt 7):270-275.

PMID: 35787554 PMC: 9254895. DOI: 10.1107/S2053230X22006586.

High-Titer Production of the Fungal Anhydrotetracycline, TAN-1612, in Engineered Yeasts.

Baldera-Aguayo P, Lee A, Cornish V ACS Synth Biol. 2022; 11(7):2429-2444.

PMID: 35699947 PMC: 9480237. DOI: 10.1021/acssynbio.2c00116.

Heterologous Catalysis of the Final Steps of Tetracycline Biosynthesis by .

Herbst E, Lee A, Tang Y, Snyder S, Cornish V ACS Chem Biol. 2021; 16(8):1425-1434.

PMID: 34269557 PMC: 8896654. DOI: 10.1021/acschembio.1c00259.

References

Cooke H, Guenther E, Luo Y, Shen B, Bruner S . Molecular basis of substrate promiscuity for the SAM-dependent O-methyltransferase NcsB1, involved in the biosynthesis of the enediyne antitumor antibiotic neocarzinostatin. Biochemistry. 2009; 48(40):9590-8. PMC: 4500170. DOI: 10.1021/bi901257q. View

Hatsu M, Sasaki T, Gomi S, Kodama Y, Sezaki M, Inouye S . A new tetracycline antibiotic with antitumor activity. II. The structural elucidation of SF2575. J Antibiot (Tokyo). 1992; 45(3):325-30. DOI: 10.7164/antibiotics.45.325. View

Datsenko K, Wanner B . One-step inactivation of chromosomal genes in Escherichia coli K-12 using PCR products. Proc Natl Acad Sci U S A. 2000; 97(12):6640-5. PMC: 18686. DOI: 10.1073/pnas.120163297. View

Jung W, Jeong S, Park S, Choi C, Park B, Park J . Enhanced heterologous production of desosaminyl macrolides and their hydroxylated derivatives by overexpression of the pikD regulatory gene in Streptomyces venezuelae. Appl Environ Microbiol. 2008; 74(7):1972-9. PMC: 2292611. DOI: 10.1128/AEM.02296-07. View

Binnie C, Warren M, Butler M . Cloning and heterologous expression in Streptomyces lividans of Streptomyces rimosus genes involved in oxytetracycline biosynthesis. J Bacteriol. 1989; 171(2):887-95. PMC: 209679. DOI: 10.1128/jb.171.2.887-895.1989. View

Lozano M, Remsing L, Quiros L, Brana A, Fernandez E, Sanchez C . Characterization of two polyketide methyltransferases involved in the biosynthesis of the antitumor drug mithramycin by Streptomyces argillaceus. J Biol Chem. 2000; 275(5):3065-74. DOI: 10.1074/jbc.275.5.3065. View

Petkovic H, Cullum J, Hranueli D, Hunter I, Peric-Concha N, Pigac J . Genetics of Streptomyces rimosus, the oxytetracycline producer. Microbiol Mol Biol Rev. 2006; 70(3):704-28. PMC: 1594589. DOI: 10.1128/MMBR.00004-06. View

Sum P, Ross A, Petersen P, Testa R . Synthesis and antibacterial activity of 9-substituted minocycline derivatives. Bioorg Med Chem Lett. 2005; 16(2):400-3. DOI: 10.1016/j.bmcl.2005.09.078. View

Baltz R, Miao V, Wrigley S . Natural products to drugs: daptomycin and related lipopeptide antibiotics. Nat Prod Rep. 2005; 22(6):717-41. DOI: 10.1039/b416648p. View

10.

Chen Y, Wendt-Pienkowski E, Shen B . Identification and utility of FdmR1 as a Streptomyces antibiotic regulatory protein activator for fredericamycin production in Streptomyces griseus ATCC 49344 and heterologous hosts. J Bacteriol. 2008; 190(16):5587-96. PMC: 2519381. DOI: 10.1128/JB.00592-08. View

11.

Zhang W, Watanabe K, Cai X, Jung M, Tang Y, Zhan J . Identifying the minimal enzymes required for anhydrotetracycline biosynthesis. J Am Chem Soc. 2008; 130(19):6068-9. DOI: 10.1021/ja800951e. View

12.

Wells J, OSullivan J, Aklonis C, Ax H, Tymiak A, Kirsch D . Dactylocyclines, novel tetracycline derivatives produced by a Dactylosporangium sp. I. Taxonomy, production, isolation and biological activity. J Antibiot (Tokyo). 1992; 45(12):1892-8. DOI: 10.7164/antibiotics.45.1892. View

13.

Peric-Concha N, Borovicka B, Long P, Hranueli D, Waterman P, Hunter I . Ablation of the otcC gene encoding a post-polyketide hydroxylase from the oxytetracyline biosynthetic pathway in Streptomyces rimosus results in novel polyketides with altered chain length. J Biol Chem. 2005; 280(45):37455-60. DOI: 10.1074/jbc.M503191200. View

14.

Nelson M, Levy S . The history of the tetracyclines. Ann N Y Acad Sci. 2011; 1241:17-32. DOI: 10.1111/j.1749-6632.2011.06354.x. View

15.

Wong F, Khosla C . Combinatorial biosynthesis of polyketides--a perspective. Curr Opin Chem Biol. 2012; 16(1-2):117-23. PMC: 3328608. DOI: 10.1016/j.cbpa.2012.01.018. View

16.

Stevens D, Henry M, Murphy K, Boddy C . Heterologous expression of the oxytetracycline biosynthetic pathway in Myxococcus xanthus. Appl Environ Microbiol. 2010; 76(8):2681-3. PMC: 2849223. DOI: 10.1128/AEM.02841-09. View

17.

Xue Q, Ashley G, Hutchinson C, Santi D . A multiplasmid approach to preparing large libraries of polyketides. Proc Natl Acad Sci U S A. 1999; 96(21):11740-5. PMC: 18356. DOI: 10.1073/pnas.96.21.11740. View

18.

Gust B, Challis G, Fowler K, Kieser T, Chater K . PCR-targeted Streptomyces gene replacement identifies a protein domain needed for biosynthesis of the sesquiterpene soil odor geosmin. Proc Natl Acad Sci U S A. 2003; 100(4):1541-6. PMC: 149868. DOI: 10.1073/pnas.0337542100. View

19.

Pickens L, Sawaya M, Rasool H, Pashkov I, Yeates T, Tang Y . Structural and biochemical characterization of the salicylyl-acyltranferase SsfX3 from a tetracycline biosynthetic pathway. J Biol Chem. 2011; 286(48):41539-41551. PMC: 3308865. DOI: 10.1074/jbc.M111.299859. View

20.

Pickens L, Kim W, Wang P, Zhou H, Watanabe K, Gomi S . Biochemical analysis of the biosynthetic pathway of an anticancer tetracycline SF2575. J Am Chem Soc. 2009; 131(48):17677-89. PMC: 2800175. DOI: 10.1021/ja907852c. View