Genetic dissection of the biosynthetic route to gentamicin A2 by heterologous expression of its minimal gene set

Proceedings of the National Academy of Sciences of the United States of America

Volumn 105, Issue 24, 2008, Pages 8399-8404

  Je, Won Park ^a   Hong, Jay Sung Joong ^b   Parajuli, Niranjan ^a   Won, Seok Jung ^b   Sung, Ryeol Park ^a   Lim, Si Kyu ^c   Jae, Kyung Sohng ^d   Yeo, Joon Yoon ^a  

^a Ewha Womans University   (South Korea)

^b Seoul National University   (South Korea)

^c Genotech Corporations   (South Korea)

^d SunMoon University   (South Korea)

Author keywords

Aminoglycoside biosynthesis; Micromonospora echinospora; Pathway engineering; Streptomyces venezuelae

Indexed keywords

2 DEOXYSTREPTAMINE; 2' N ACETYLPAROMAMINE; ACETIC ACID DERIVATIVE; AMINOGLYCOSIDE ANTIBIOTIC AGENT; GENTAMICIN; GENTAMYCIN A2; GLYCOSYLTRANSFERASE; N ACETYLGLUCOSAMINE; PROTEIN GTME; STREPTOMYCIN; TRISACCHARIDE; XYLOSE;

ACTINOBACTERIA; ARTICLE; BACTERIAL STRAIN; BIOSYNTHESIS; GACH GENE; GENE CLUSTER; GENE EXPRESSION; GENE FUNCTION; GENETIC MANIPULATION; GTMA GENE; GTMB GENE; GTNM GENE; MICROMONOSPHORA ECHINOSPORA; MICROMONOSPORA; NONHUMAN; NUCLEOTIDE SEQUENCE; PRIORITY JOURNAL; STREPTOMYCES VENEZUELAE;

AMINOGLYCOSIDES; BASE SEQUENCE; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; DISACCHARIDES; DRUG RESISTANCE, BACTERIAL; GENE EXPRESSION; GENES, BACTERIAL; GENTAMICINS; HEXOSAMINES; MICROMONOSPORA; MOLECULAR SEQUENCE DATA; MULTIGENE FAMILY; N-ACYLSPHINGOSINE GALACTOSYLTRANSFERASE; SPECTROMETRY, MASS, ELECTROSPRAY IONIZATION; STREPTOMYCES;

ACTINOBACTERIA (CLASS); BACTERIA (MICROORGANISMS); MICROMONOSPORA ECHINOSPORA; STREPTOMYCES VENEZUELAE;

EID: 46149125940     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.0803164105     Document Type: Article

References (35)

1. Weinstein MJ, Luedemann GM, Oden EM, Wagman GH (1963) Gentamicin, a new antibiotic complex from Micromonospora. Antimicrob Agents Chemother 122:463-464.
2. Carter AP, et al. (2000) Functional insights from the structure of the 30S ribosomal subunit and its interactions with antibiotics. Nature 407:340-348.
3. Schatz A, Bugie E, Waksman SA (1944) Streptomycin, a substance exhibiting antibiotic activity against gram-positive and gram-negative bacteria. Proc Soc Exp Med Biol 55:66-69.
4. Testa RT, Tilley BC (1976) Biotransformation, a new approach to aminoglycoside biosynthesis: II. Gentamicin. J Antibiot 29:140-146.
5. Ota Y, et al. (2000) Butirosin-biosynthetic gene cluster from Bacillus circulans. J Antibiot 53:1158-1167.
6. Huang F, et al. (2005) The neomycin biosynthetic gene cluster of Streptomyces fradiae NCIMB 8233: Characterisation of an aminotransferase involved in the formation of 2-deoxystreptamine. Org Biomol Chem 3:1410-1418.
7. Huang F, et al. (2007) Elaboration of neosamine rings in the biosynthesis of neomycin and butirosin. ChemBioChem 8:283-288.
8. Llewellyn NM, Li Y, Spencer JB (2007) Biosynthesis of butirosin: transfer and deprotection of the unique amino acid side chain. Chem Biol 14:379-386.
9. Kudo F, Fujii T, Kinoshita S, Eguchi T (2007) Unique O-ribosylation in the biosynthesis of butirosin. Bioorg Med Chem 15:4360-4368.
10. Kharel MK, et al. (2004) A gene cluster for biosynthesis of kanamycin from Streptomyces kanamyceticus: Comparison with gentamicin biosynthetic gene cluster. Arch Biochem Biophys 429:204-214.
11. Unwin J, et al. (2004) Gene cluster in Micromonospora echinospora ATCC 15835 for the biosynthesis of the gentamicin C complex. J Antibiot 57:436-445.
12. Kharel MK, et al. (2004) Molecular cloning and characterization of a 2-deoxystreptamine biosynthetic gene cluster in gentamicin-producing Micromonospora echinospora ATCC 15835. Mol Cells 18:71-78.
13. Kharel MK, et al. (2004) Isolation and characterization of the tobramycin biosynthetic gene cluster from Streptomyces tenebrarius. FEMS Microbiol Lett 230:185-190.
14. Love SF, Maiese WM, Rothstein DM (1992) Conditions for protoplasting, regenerating, and transforming the calicheamicin producer, Micromonospora echinospora. Appl Environ Microbiol 58:1376-1378.
15. Llewellyn NM, Spencer JB (2006) Biosynthesis of 2-deoxystreptamine- containing aminoglycoside antibiotics. Nat Prod Rep 23:864-874.
16. Testa RT, Tilley BC (1979) Biosynthesis of sisomicin and gentamicin. Jpn J Antibiot 32 Suppl:S47-S59.
17. Kase H, Odakura Y, Nakayama K (1982) Sagamicin and the related aminoglycosides: fermentation and biosynthesis. I. Biosynthetic studies with the blocked mutants of Micromonospora sagamiensis. J Antibiot 35:1-9.
18. Truman AW, Huang F, Llewellyn NM, Spencer JB (2007) Characterization of the enzyme BtrD from Bacillus circulans and revision of its functional assignment in the biosynthesis of butirosin. Angew Chem Int Ed 46:1462-1464.
19. Smirnova N, Reynolds KA (2001) Engineered fatty acid biosynthesis in Streptomyces by altered catalytic function of beta-ketoacyl-acyl carrier protein synthase III. J Bacteriol 183:2335-2342.
20. Hong JSJ, et al. (2004) New olivosyl derivatives of methymycin/pikromycin from an engineered strain of Streptomyces venezuelae. FEMS Microbiol Lett 238:391-399.
21. Huang F, Li Y, Yu J, Spencer JB (2002) Biosynthesis of aminoglycoside antibiotics: Cloning, expression and characterisation of an aminotransferase involved in the pathway to 2-deoxystreptamine. Chem Commun 7:2860-2861.
22. Kudo F, et al. (2005) Biosynthesis of 2-deoxystreptamine by three crucial enzymes in Streptomyces fradiae NBRC 12773. J Antibiot 58:766-774.
23. Yokoyama K, et al. (2005) Stereochemical recognition of doubly functional aminotransferase in 2-deoxystreptamine biosynthesis. J Am Chem Soc 127:5869-5874.
24. Yokoyama K, et al. (2007) Characterization and mechanistic study of a radical SAM dehydrogenase in the biosynthesis of butirosin. J Am Chem Soc 129:15147-15155.
25. Park JW, et al. (2007) Analytical profiling of biosynthetic intermediates involved in the gentamicin pathway of Micromonospora echinospora by high-performance liquid chromatography using electrospray ionization mass spectrometric detection. Anal Chem 79:4860-4869.
26. Rinehart KL, Jr (1979) Biosynthesis and mutasynthesis of aminocyclitol antibiotics. Jpn J Antibiot 32 Suppl:S32-S46.
27. Hofmann C, et al. (2005) Genes encoding enzymes responsible for biosynthesis of L-lyxose and attachment of eurekanate during avilamycin biosynthesis. Chem Biol 12:1137-1143.
28. Bililign T, Shepard EM, Ahlert J, Thorson JS (2002) On the origin of deoxypentoses: Evidence to support a glucose progenitor in the biosynthesis of calicheamicin. ChemBioChem 3:1143-1146.
29. Harper AD, Bar-Peled M (2002) Biosynthesis of UDP-xylose. Cloning and characterization of a novel Arabidopsis gene family, UXS, encoding soluble and putative membrane-bound UDP-glucuronic acid decarboxylase isoforms Plant Physiol 130:2188-2198.
30. Bar-Peled M, Griffith CL, Doering TL (2001) Functional cloning and characterization of a UDP-glucuronic acid decarboxylase: The pathogenic fungus Cryptococcus neoformans elucidates UDP-xylose synthesis. Proc Natl Acad Sci USA 98:12003-12008.
31. Kieser T, et al. (2000) in Practical Streptomyces Genetics (John Innes Foundation, Norwich, UK), pp 75-97.
32. 4. J Org Chem 40:2830-2834.
33. 2. J Org Chem 40:2835-2836.
34. Haskell TH, French JC, Bartz QR (1959) Paromomycin. I. Paromamine, a glycoside of D-glucosamine. J Am Chem Soc 81:3480-3481.
35. Lee HC, Lee SD, Sohng JK, Liou K (2004) One-pot enzymatic synthesis of UDP-D-glucose from UMP and glucose-1-phosphate using an ATP regeneration system. J Biochem Mol Biol 37:503-506.