Biosynthetic study of cephalosporin p1 reveals a multifunctional p450 enzyme and a site-selective acetyltransferase

ACS Chemical Biology

Volumn 15, Issue 1, 2020, Pages 44-51

  Cao, Zhi Qin ^a,b   Lv, Jian Ming ^a   Liu, Qiu ^a   Qin, Sheng Ying ^c   Chen, Guo Dong ^a   Dai, Ping ^a   Zhong, Yue ^b   Gao, Hao ^a   Yao, Xin Sheng ^a   Hu, Dan ^a  

^a JINAN UNIVERSITY   (China)

^b SHENZHEN INSTITUTES OF ADVANCED TECHNOLOGY   (China)

^c THE FIRST AFFILIATED HOSPITAL OF JINAN UNIVERSITY   (China)

Author keywords

[No Author keywords available]

Indexed keywords

ACYLTRANSFERASE; CEPHALOSPORIN DERIVATIVE; CEPHALOSPORIN P1; CYTOCHROME P450; FUSIDIC ACID; SHORT CHAIN DEHYDROGENASE/REDUCTASE; UNCLASSIFIED DRUG; CARBONYL REDUCTASE; HELVOLIC ACID; MULTIFUNCTIONAL ENZYME;

ANTIBACTERIAL ACTIVITY; ANTIBIOTIC BIOSYNTHESIS; ARTICLE; ASPERGILLUS ORYZAE; CHEMICAL STRUCTURE; GENE CLUSTER; HETEROLOGOUS EXPRESSION; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; MINIMUM INHIBITORY CONCENTRATION; OXYGENATION; PRIORITY JOURNAL; ACETYLATION; BIOSYNTHESIS; CHEMISTRY; ENZYME ACTIVE SITE; GENE EXPRESSION REGULATION; GENETICS; HYDROXYLATION; METABOLISM; MOLECULAR CLONING; NUCLEOTIDE SEQUENCE; OXIDATION REDUCTION REACTION;

ACETYLATION; ACETYLTRANSFERASES; ASPERGILLUS ORYZAE; BASE SEQUENCE; CARBONYL REDUCTASE (NADPH); CATALYTIC DOMAIN; CEPHALOSPORINS; CLONING, MOLECULAR; CYTOCHROME P-450 ENZYME SYSTEM; FUSIDIC ACID; GENE EXPRESSION REGULATION; HYDROXYLATION; MOLECULAR STRUCTURE; MULTIFUNCTIONAL ENZYMES; OXIDATION-REDUCTION;

EID: 85077675123     PISSN: 15548929     EISSN: 15548937     Source Type: Journal    
DOI: 10.1021/acschembio.9b00863     Document Type: Article

References (22)

1. Zhao, M., Gödecke, T., Gunn, J., Duan, J. A., and Che, C. T. (2013) Protostane and fusidane triterpenes: A mini-review. Molecules 18, 4054-4080, 10.3390/molecules18044054
2. Godtfredsen, W. O., Jahnsen, S., Lorck, H., Roholt, K., and Tybring, L. (1962) Fusidic acid: A new antibiotic. Nature 193, 987, 10.1038/193987a0
3. Jones, R. N., Mendes, R. E., Sader, H. S., and Castanheira, M. (2011) In vitro antimicrobial findings for fusidic acid tested against contemporary (2008-2009) Gram-positive organisms collected in the United States. Clin. Infect. Dis. 52, S477-S486, 10.1093/cid/cir163
4. Zhou, J., Lancaster, L., Donohue, J. P., and Noller, H. F. (2013) Crystal structures of EF-G-ribosome complexes trapped in intermediate states of translocation. Science 340, 1236086, 10.1126/science.1236086
5. Bodley, J. W., Zieve, F. J., Lin, L., and Zieve, S. T. (1969) Formation of the ribosome-G factor-GDP complex in the presence of fusidic acid. Biochem. Biophys. Res. Commun. 37, 437-443, 10.1016/0006-291X(69)90934-6
6. Wilson, D. N. (2014) Ribosome-Targeting antibiotics and mechanisms of bacterial resistance. Nat. Rev. Microbiol. 12, 35-48, 10.1038/nrmicro3155
7. Ibrahim, A. R. S. and Ragab, A. E. (2018) Fusidic acid ring B hydroxylation by Cunninghamella elegans. Phytochem. Lett. 25, 86-89, 10.1016/j.phytol.2018.04.003
8. Von Daehne, W., Godtfredsen, W. O., and Rasmussen, P. R. (1979) Structure-Activity relationships in fusidic acid-Type antibiotics. Adv. Appl. Microbiol. 25, 95-146, 10.1016/S0065-2164(08)70148-5
9. Duvold, T., Jørgensen, A., Andersen, N. R., Henriksen, A. S., Dahl Sørensen, M., and Björkling, F. (2002) 17 S,20 S-methanofusidic acid, a new potent semi-synthetic fusidane antibiotic. Bioorg. Med. Chem. Lett. 12, 3569-3572, 10.1016/S0960-894X(02)00797-7
10. Duvold, T., Sørensen, M. D., Björkling, F., Henriksen, A. S., and Rastrup-Andersen, N. (2001) Synthesis and conformational analysis of fusidic acid side chain derivatives in relation to antibacterial activity. J. Med. Chem. 44, 3125-3131, 10.1021/jm010899a
11. Mitsuguchi, H., Seshime, Y., Fujii, I., Shibuya, M., Ebizuka, Y., and Kushiro, T. (2009) Biosynthesis of steroidal antibiotic fusidanes: functional analysis of oxidosqualene cyclase and subsequent tailoring enzymes from Aspergillus fumigatus. J. Am. Chem. Soc. 131, 6402-6411, 10.1021/ja8095976
12. Lodeiro, S., Xiong, Q., Wilson, W. K., Ivanova, Y., Smith, M. L., May, G. S., and Matsuda, S. P. (2009) Protostadienol biosynthesis and metabolism in the pathogenic fungus Aspergillus fumigatus. Org. Lett. 11, 1241-1244, 10.1021/ol802696a
13. Lv, J. M., Hu, D., Gao, H., Kushiro, T., Awakawa, T., Chen, G. D., Wang, C. X., Abe, I., and Yao, X. S. (2017) Biosynthesis of helvolic acid and identification of an unusual C-4-demethylation process distinct from sterol biosynthesis. Nat. Commun. 8, 1644, 10.1038/s41467-017-01813-9
14. Cao, Z. Q., Li, S. Y., Lv, J. M., Gao, H., Chen, G. D., Awakawa, T., Abe, I., Yao, X. S., and Hu, D. (2019) Biosynthesis of clinically used antibiotic fusidic acid and identification of two short-chain dehydrogenase/reductases with converse stereoselectivity. Acta Pharm. Sin. B 9, 433-442, 10.1016/j.apsb.2018.10.007
15. Gutiérrez, S., Velasco, J., Fernandez, F. J., and Martín, J. F. (1992) The cefG gene of Cephalosporium acremonium is linked to the cefEF gene and encodes a deacetylcephalosporin C acetyltransferase closely related to homoserine O-Acetyltransferase. J. Bacteriol. 174, 3056-3064, 10.1128/jb.174.9.3056-3064.1992
16. Chou, T. S., Eisenbraun, E. J., and Rapala, R. T. (1969) The chemistry of steroid acids from Cephalosporium acremonium. Tetrahedron 25, 3341-3357, 10.1016/S0040-4020(01)82867-2
17. Lin, H. C., Tsunematsu, Y., Dhingra, S., Xu, W., Fukutomi, M., Chooi, Y. H., Cane, D. E., Calvo, A. M., Watanabe, K., and Tang, Y. (2014) Generation of complexity in fungal terpene biosynthesis: discovery of a multifunctional cytochrome P450 in the fumagillin pathway. J. Am. Chem. Soc. 136, 4426-4436, 10.1021/ja500881e
18. Huang, J. H., Lv, J. M., Wang, Q. Z., Zou, J., Lu, Y. J., Wang, Q. L., Chen, D. N., Yao, X. S., Gao, H., and Hu, D. (2019) Biosynthesis of an anti-Tuberculosis sesterterpenoid asperterpenoid A. Org. Biomol. Chem. 17, 248-251, 10.1039/C8OB02832J
19. Geisler, K., Hughes, R. K., Sainsbury, F., Lomonossoff, G. P., Rejzek, M., Fairhurst, S., Olsen, C. E., Motawia, M. S., Melton, R. E., Hemmings, A. M., Bak, S., and Osbourn, A. (2013) Biochemical analysis of a multifunctional cytochrome P450 (CYP51) enzyme required for synthesis of antimicrobial triterpenes in plants. Proc. Natl. Acad. Sci. U. S. A. 110, E3360-3367, 10.1073/pnas.1309157110
20. Wang, G. Q., Chen, G. D., Qin, S. Y., Hu, D., Awakawa, T., Li, S. Y., Lv, J. M., Wang, C. X., Yao, X. S., Abe, I., and Gao, H. (2018) Biosynthetic pathway for furanosteroid demethoxyviridin and identification of an unusual pregnane side-chain cleavage. Nat. Commun. 9, 1838, 10.1038/s41467-018-04298-2
21. Zhang, S., Wang, S., Zhang, Q., Chang, C. W. T., and Zhan, J. (2015) Three new fusidic acid derivatives and their antibacterial activity. Bioorg. Med. Chem. Lett. 25, 1920-1924, 10.1016/j.bmcl.2015.03.033
22. Dai, P., Wang, C. X., Gao, H., Wang, Q. Z., Tang, X. L., Chen, G. D., Hong, K., Hu, D., and Yao, X. S. (2017) Characterization of methyltransferase AlmCII in chalcomycin biosynthesis: The first TylF family O-methyltransferase works on a 4'-deoxysugar. ChemBioChem 18, 1510-1517, 10.1002/cbic.201700216