Genome neighborhood network reveals insights into enediyne biosynthesis and facilitates prediction and prioritization for discovery
详细信息 查看全文
- 作者：Jeffrey D. Rudolf ; Xiaohui Yan ; Ben Shen
- 关键词：Enediyne polyketide synthase ; Genome neighborhood network ; Biosynthetic gene cluster ; Genome mining ; Natural products
- 刊名：Journal of Industrial Microbiology and Biotechnology
- 出版年：2016
- 出版时间：March 2016
- 年：2016
- 卷：43
- 期：2-3
- 页码：261-276
- 全文大小：7,594 KB
- 参考文献：1.Ahlert J, Shepard E, Lomovskaya N, Zazopoulos E, Staffa A, Bachmann BO, Huang K, Fonstein L, Czisny A, Whitwam RE, Farnet CM, Thorson JS (2002) The calicheamicin gene cluster and its iterative type I enediyne PKS. Science 297:1173–1176. doi:10.1126/science.1072105 CrossRef PubMed
2.Belecki K, Crawford JM, Townsend CA (2009) Production of octaketide polyenes by the calicheamicin polyketide synthase CalE8: implications for the biosynthesis of enediyne core structures. J Am Chem Soc 131:12564–12566. doi:10.1021/ja904391r PubMedCentral CrossRef PubMed
3.Boghaert ER, Sridharan L, Armellino DC, Khandke KM, DiJoseph JF, Kunz A, Dougher MM, Jiang F, Kalyandrug LB, Hamann PR, Frost P, Damle NK (2004) Antibody-targeted chemotherapy with the calicheamicin conjugate hu3S193-N-acetyl γ calicheamicin dimethyl hydrazide targets Lewisy and eliminates Lewisy-positive human carcinoma cells and xenografts. Clin Cancer Res 10:4538–4549. doi:10.1158/1078-0432.ccr-04-0037 CrossRef PubMed
4.Brown SD, Babbitt PC (2012) Inference of functional properties from large-scale analysis of enzyme superfamilies. J Biol Chem 287:35–42. doi:10.1074/jbc.R111.283408 PubMedCentral CrossRef PubMed
5.Buchanan GO, Williams PG, Feling RH, Kauffman CA, Jensen PR, Fenical W (2005) Sporolides A and B: structurally unprecedented halogenated macrolides from the marine actinomycete Salinispora tropica. Org Lett 7:2731–2734. doi:10.1021/ol050901i CrossRef PubMed
6.Camacho C, Coulouris G, Avagyan V, Ma N, Papadopoulos J, Bealer K, Madden Thomas L (2009) BLAST+: architecture and applications. BMC Bioinformatics 10:421. doi:10.1186/1471-2105-10-421 PubMedCentral CrossRef PubMed
7.Chari RVJ (2008) Targeted cancer therapy: conferring specificity to cytotoxic drugs. Acc Chem Res 41:98–107. doi:10.1021/ar700108g CrossRef PubMed
8.Chow J-Y, Tian B-X, Ramamoorthy G, Hillerich BS, Seidel RD, Almo SC, Jacobson MP, Poulter CD (2015) Computational-guided discovery and characterization of a sesquiterpene synthase from Streptomyces clavuligerus. Proc Natl Acad Sci USA 112:5661–5666. doi:10.1073/pnas.1505127112 PubMedCentral CrossRef PubMed
9.Davies J, Wang H, Taylor T, Warabi K, Huang X-H, Andersen RJ (2005) Uncialamycin, a new enediyne antibiotic. Org Lett 7:5233–5236. doi:10.1021/ol052081f CrossRef PubMed
10.Dedon PC, Goldberg IH (1990) Sequence-specific double-strand breakage of DNA by neocarzinostatin involves different chemical mechanisms within a staggered cleavage site. J Biol Chem 265:14713–14716PubMed
11.Edo K, Mizugaki M, Koide Y, Seto H, Furihata K, Otake N, Ishida N (1985) The structure of neocarzinostatin chromophore possessing a novel bicyclo[7.3.0]dodecadiyne system. Tetrahedron Lett 26:331–334. doi:10.1016/s0040-4039(01)80810-8 CrossRef
12.Elshahawi SI, Ramelot TA, Seetharaman J, Chen J, Singh S, Yang Y, Pederson K, Kharel MK, Xiao R, Lew S, Yennamalli RM, Miller MD, Wang F, Tong L, Montelione GT, Kennedy MA, Bingman CA, Zhu H, Phillips GN, Thorson JS (2014) Structure-guided functional characterization of enediyne self-sacrifice resistance proteins, CalU16 and CalU19. ACS Chem Biol 9:2347–2358. doi:10.1021/cb500327m PubMedCentral CrossRef PubMed
13.Galm U, Hager MH, Van Lanen SG, Ju J, Thorson JS, Shen B (2005) Antitumor antibiotics: bleomycin, enediynes, and mitomycin. Chem Rev 105:739–758. doi:10.1021/cr030117g CrossRef PubMed
14.Gao Q, Thorson JS (2008) The biosynthetic genes encoding for the production of the dynemicin enediyne core in Micromonospora chersina ATCC53710. FEMS Microbiol Lett 282:105–114. doi:10.1111/j.1574-6968.2008.01112.x CrossRef PubMed
15.Golik J, Dubay G, Groenewold G, Kawaguchi H, Konishi M, Krishnan B, Ohkuma H, Saitoh K, Doyle TW (1987) Esperamicins, a novel class of potent antitumor antibiotics. 3. Structures of esperamicins A1, A2, and A1b. J Am Chem Soc 109:3462–3464. doi:10.1021/ja00245a049 CrossRef
16.Hall TA (1999) BioEdit: a user-friendly biological sequence alignment editor and analysis program for Windows 95/98/NT. Nucl Acids Symp Ser 41:95–98
17.Hirama M, Akiyama K, Tanaka T, Noda T, K-I Iida, Sato I, Hanaishi R, Fukuda-Ishisaka S, Ishiguro M, Otani T, Leet JE (2000) Paramagnetic enediyne antibiotic C-1027: spin identification and characterization of radical species. J Am Chem Soc 122:720–721. doi:10.1021/ja993256h CrossRef
18.Horsman GP, Chen Y, Thorson JS, Shen B (2010) Polyketide synthase chemistry does not direct biosynthetic divergence between 9- and 10-membered enediynes. Proc Natl Acad Sci USA 107:11331–11335. doi:10.1073/pnas.1003442107 PubMedCentral CrossRef PubMed
19.Horsman GP, Lechner A, Ohnishi Y, Moore BS, Shen B (2013) Predictive model for epoxide hydrolase-generated stereochemistry in the biosynthesis of nine-membered enediyne antitumor antibiotics. Biochemistry 52:5217–5224. doi:10.1021/bi400572a CrossRef PubMed
20.Jones RR, Bergman RG (1972) p-Benzyne. Generation as an intermediate in a thermal isomerization reaction and trapping evidence for the 1,4-benzenediyl structure. J Am Chem Soc 94:660–661. doi:10.1021/ja00757a071 CrossRef
21.Kennedy DR, Ju J, Shen B, Beerman TA (2007) Designer enediynes generate DNA breaks, interstrand cross-links, or both, with concomitant changes in the regulation of DNA damage responses. Proc Natl Acad Sci USA 104:17632–17637. doi:10.1073/pnas.0708274104 PubMedCentral CrossRef PubMed
22.Kobayashi S, Ashizawa S, Takahashi Y, Sugiura Y, Nagaoka M, Lear MJ, Hirama M (2001) The first total synthesis of N1999-A2: absolute stereochemistry and stereochemical implications into DNA cleavage. J Am Chem Soc 123:11294–11295. doi:10.1021/ja011779v CrossRef PubMed
23.Komano K, Shimamura S, Norizuki Y, Zhao D, Kabuto C, Sato I, Hirama M (2009) Total synthesis and structure revision of the (−)-maduropeptin chromophore. J Am Chem Soc 131:12072–12073. doi:10.1021/ja905397p CrossRef PubMed
24.Kong R, Goh LP, Liew CW, Ho QS, Murugan E, Li B, Tang K, Liang Z-X (2008) Characterization of a carbonyl-conjugated polyene precursor in 10-membered enediyne biosynthesis. J Am Chem Soc 130:8142–8143. doi:10.1021/ja8019643 CrossRef PubMed
25.Lane AL, Nam S-J, Fukuda T, Yamanaka K, Kauffman CA, Jensen PR, Fenical W, Moore BS (2013) Structures and comparative characterization of biosynthetic gene clusters for cyanosporasides, enediyne-derived natural products from marine actinomycetes. J Am Chem Soc 135:4171–4174. doi:10.1021/ja311065v PubMedCentral CrossRef PubMed
26.Lee MD, Dunne TS, Chang CC, Ellestad GA, Siegel MM, Morton GO, McGahren WJ, Borders DB (1987) Calichemicins, a novel family of antitumor antibiotics. 2. Chemistry and structure of calichemicin γ1I. J Am Chem Soc 109:3466–3468. doi:10.1021/ja00245a051 CrossRef
27.Liang Z-X (2010) Complexity and simplicity in the biosynthesis of enediyne natural products. Nat Prod Rep 27:499–528. doi:10.1039/b908165h CrossRef PubMed
28.Lin S, Horsman GP, Chen Y, Li W, Shen B (2009) Characterization of the SgcF epoxide hydrolase supporting an (R)-vicinal diol intermediate for enediyne antitumor antibiotic C-1027 biosynthesis. J Am Chem Soc 131:16410–16417. doi:10.1021/ja901242s PubMedCentral CrossRef PubMed
29.Liu W, Christenson SD, Standage S, Shen B (2002) Biosynthesis of the enediyne antitumor antibiotic C-1027. Science 297:1170–1173. doi:10.1126/science.1072110 CrossRef PubMed
30.Liu W, Ahlert J, Gao Q, Wendt-Pienkowski E, Shen B, Thorson JS (2003) Rapid PCR amplification of minimal enediyne polyketide synthase cassettes leads to a predictive familial classification model. Proc Natl Acad Sci USA 100:11959–11963. doi:10.1073/pnas.2034291100 PubMedCentral CrossRef PubMed
31.Liu W, Nonaka K, Nie L, Zhang J, Christenson SD, Bae J, Van Lanen SG, Zazopoulos E, Farnet CM, Yang CF, Shen B (2005) The neocarzinostatin biosynthetic gene cluster from Streptomyces carzinostaticus ATCC 15944 involving two iterative type I polyketide synthases. Chem Biol 12:293–302. doi:10.1016/j.chembiol.2004.12.013 CrossRef PubMed
32.Lohman JR, Huang S-X, Horsman GP, Dilfer PE, Huang T, Chen Y, Wendt-Pienkowski E, Shen B (2013) Cloning and sequencing of the kedarcidin biosynthetic gene cluster from Streptoalloteichus sp. ATCC 53650 revealing new insights into biosynthesis of the enediyne family of antitumor antibiotics. Mol Biosyst 9:478–491. doi:10.1039/c3mb25523a PubMedCentral CrossRef PubMed
33.McDonald LA, Capson TL, Krishnamurthy G, Ding W-D, Ellestad GA, Bernan VS, Maiese WM, Lassota P, Discafani C et al (1996) Namenamicin, a new enediyne antitumor antibiotic from the marine ascidian Polysyncraton lithostrotum. J Am Chem Soc 118:10898–10899. doi:10.1021/ja961122n CrossRef
34.McGlinchey RP, Nett M, Moore BS (2008) Unraveling the biosynthesis of the sporolide cyclohexenone building block. J Am Chem Soc 130:2406–2407. doi:10.1021/ja710488m CrossRef PubMed
35.Myers AG (1987) Proposed structure of the neocarzinostatin chromophore-methyl thioglycolate adduct; a mechanism for the nucleophilic activation of neocarzinostatin. Tetrahedron Lett 28:4493–4496. doi:10.1016/s0040-4039(00)96545-6 CrossRef
36.Myers AG, Fraley ME, Tom NJ, Cohen SB, Madar DJ (1995) Synthesis of (+)-dynemicin A and analogs of wide structural variability: establishment of the absolute configuration of natural dynemicin A. Chem Biol 2:33–43. doi:10.1016/1074-5521(95)90078-0 CrossRef PubMed
37.Nam S-J, Gaudencio SP, Kauffman CA, Jensen PR, Kondratyuk TP, Marler LE, Pezzuto JM, Fenical W (2010) Fijiolides A and B, inhibitors of TNF-α-induced NFκB activation, from a marine-derived sediment bacterium of the genus Nocardiopsis. J Nat Prod 73:1080–1086. doi:10.1021/np100087c PubMedCentral CrossRef PubMed
38.Oh D-C, Williams PG, Kauffman CA, Jensen PR, Fenical W (2006) Cyanosporasides A and B, chloro- and cyano-cyclopenta[a]indene glycosides from the marine actinomycete “Salinispora pacifica”. Org Lett 8:1021–1024. doi:10.1021/ol052686b CrossRef PubMed
39.Oku N, Matsunaga S, Fusetani N (2003) Shishijimicins A–C, novel enediyne antitumor antibiotics from the ascidian Didemnum proliferum. J Am Chem Soc 125:2044–2045. doi:10.1021/ja0296780 CrossRef PubMed
40.Otani T, Yoshida K-I, Sasaki T, Minami Y (1999) C-1027 enediyne chromophore: presence of another active form and its chemical structure. J Antibiot 52:415–421. doi:10.7164/antibiotics.52.415 CrossRef PubMed
41.Ren F, Hogan PC, Anderson AJ, Myers AG (2007) Kedarcidin chromophore: synthesis of its proposed structure and evidence for a stereochemical revision. J Am Chem Soc 129:5381–5383. doi:10.1021/ja071205b PubMedCentral CrossRef PubMed
42.Rudolf JD, Dong L-B, Huang T, Shen B (2015) A genetically amenable platensimycin- and platencin-overproducer as a platform for biosynthetic explorations: a showcase of PtmO4, a long-chain acyl-CoA dehydrogenase. Mol Biosyst. doi:10.1039/C5MB00302D PubMedCentral PubMed
43.Senter PD (2009) Potent antibody drug conjugates for cancer therapy. Curr Opin Chem Biol 13:235–244. doi:10.1016/j.cbpa.2009.03.023 CrossRef PubMed
44.Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, Amin N, Schwikowski B, Ideker T (2003) Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res 13:2498–2504. doi:10.1101/gr.1239303 PubMedCentral CrossRef PubMed
45.Shen B, Hindra Yan X, Huang T, Ge H, Yang D, Teng Q, Rudolf JD, Lohman JR (2015) Enediynes: exploration of microbial genomics to discover new anticancer drug leads. Bioorg Med Chem Lett 25:9–15. doi:10.1016/j.bmcl.2014.11.019 PubMedCentral CrossRef PubMed
46.Sievers EL, Appelbaum FR, Spielberger RT, Forman SJ, Flowers D, Smith FO, Shannon-Dorcy K, Berger MS, Bernstein ID (1999) Selective ablation of acute myeloid leukemia using antibody-targeted chemotherapy: a phase I study of an anti-CD33 calicheamicin immunoconjugate. Blood 93:3678–3684PubMed
47.Sugimoto Y, Otani T, Oie S, Wierzba K, Yamada Y (1990) Mechanism of action of a new macromolecular antitumor antibiotic, C-1027. J Antibiot 43:417–421. doi:10.7164/antibiotics.43.417 CrossRef PubMed
48.Tamura K, Stecher G, Peterson D, Filipski A, Kumar S (2013) MEGA6: molecular evolutionary genetics analysis version 6.0. Mol Biol Evol 30:2725–2729. doi:10.1093/molbev/mst197 PubMedCentral CrossRef PubMed
49.Thompson JD, Higgins DG, Gibson TJ (1994) Improved sensitivity of profile searches through the use of sequence weights and gap excision. CABIOS Comput Appl Biosci 10:19–29PubMed
50.Thorson JS, Sievers EL, Ahlert J, Shepard E, Whitwam RE, Onwueme KC, Ruppen M (2000) Understanding and exploiting nature’s chemical arsenal: the past, present and future of calicheamicin research. Curr Pharm Des 6:1841–1879. doi:10.2174/1381612003398564 CrossRef PubMed
51.Van Lanen SG, Shen B (2008) Biosynthesis of enediyne antitumor antibiotics. Curr Top Med Chem 8:448–459. doi:10.2174/156802608783955656 PubMedCentral CrossRef PubMed
52.Van Lanen SG, T-j Oh, Liu W, Wendt-Pienkowski E, Shen B (2007) Characterization of the maduropeptin biosynthetic gene cluster from Actinomadura madurae ATCC 39144 supporting a unifying paradigm for enediyne biosynthesis. J Am Chem Soc 129:13082–13094. doi:10.1021/ja073275o PubMedCentral CrossRef PubMed
53.Van Lanen SG, Lin S, Horsman GP, Shen B (2009) Characterization of SgcE6, the flavin reductase component supporting FAD-dependent halogenation and hydroxylation in the biosynthesis of the enediyne antitumor antibiotic C-1027. FEMS Microbiol Lett 300:237–241. doi:10.1111/j.1574-6968.2009.01802.x PubMedCentral CrossRef PubMed
54.Zazopoulos E, Huang K, Staffa A, Liu W, Bachmann BO, Nonaka K, Ahlert J, Thorson JS, Shen B, Farnet CM (2003) A genomics-guided approach for discovering and expressing cryptic metabolic pathways. Nat Biotechnol 21:187–190. doi:10.1038/nbt784 CrossRef PubMed
55.Zhang J, Van Lanen SG, Ju J, Liu W, Dorrestein PC, Li W, Kelleher NL, Shen B (2008) A phosphopantetheinylating polyketide synthase producing a linear polyene to initiate enediyne antitumor antibiotic biosynthesis. Proc Natl Acad Sci USA 105:1460–1465. doi:10.1073/pnas.0711625105 PubMedCentral CrossRef PubMed
56.Zhang X, Kumar R, Vetting MW, Zhao S, Jacobson MP, Almo SC, Gerlt JA (2015) A unique cis-3-hydroxy-l -proline dehydratase in the enolase superfamily. J Am Chem Soc 137:1388–1391. doi:10.1021/ja5103986 CrossRef PubMed
57.Zhao S, Jacobson Matthew P, Sakai A, Zhang X, Kumar R, San Francisco B, Solbiati J, Gerlt John A, Vetting Matthew W, Hillerich B, Seidel Ronald D, Almo Steven C, Steves A, Brown S, Akiva E, Barber A, Babbitt Patricia C (2014) Prediction and characterization of enzymatic activities guided by sequence similarity and genome neighborhood networks. eLife 3:e03275. doi:10.7554/eLife.03275 PubMedCentral
58.Zhen Y, Ming X, Yu B, Otani T, Saito H, Yamada Y (1989) A new macromolecular antitumor antibiotic, C-1027. III. Antitumor activity. J Antibiot 42:1294–1298. doi:10.7164/antibiotics.42.1294 CrossRef PubMed - 作者单位：Jeffrey D. Rudolf (1)
Xiaohui Yan (1)
Ben Shen (1) (2) (3)
1. Department of Chemistry, The Scripps Research Institute, Jupiter, FL, 33458, USA
2. Department of Molecular Therapeutics, The Scripps Research Institute, Jupiter, FL, 33458, USA
3. Natural Products Library Initiative, The Scripps Research Institute, Jupiter, FL, 33458, USA - 刊物类别：Biomedical and Life Sciences
- 刊物主题：Chemistry
Biotechnology
Genetic Engineering
Biochemistry
Bioinformatics
Microbiology
Microbial Genetics and Genomics - 出版者：Springer Berlin / Heidelberg
- ISSN：1476-5535
文摘
The enediynes are one of the most fascinating families of bacterial natural products given their unprecedented molecular architecture and extraordinary cytotoxicity. Enediynes are rare with only 11 structurally characterized members and four additional members isolated in their cycloaromatized form. Recent advances in DNA sequencing have resulted in an explosion of microbial genomes. A virtual survey of the GenBank and JGI genome databases revealed 87 enediyne biosynthetic gene clusters from 78 bacteria strains, implying that enediynes are more common than previously thought. Here we report the construction and analysis of an enediyne genome neighborhood network (GNN) as a high-throughput approach to analyze secondary metabolite gene clusters. Analysis of the enediyne GNN facilitated rapid gene cluster annotation, revealed genetic trends in enediyne biosynthetic gene clusters resulting in a simple prediction scheme to determine 9- versus 10-membered enediyne gene clusters, and supported a genomic-based strain prioritization method for enediyne discovery. Keywords Enediyne polyketide synthase Genome neighborhood network Biosynthetic gene cluster Genome mining Natural products