Folate biosynthesis pathway: mechanisms and insights into drug design for infectious diseases

Author(s)

Bertacine Dias, Marcio V. ^{[1, 2, 3]} ; Santos, Jademilson C. ^[1] ; Libreros-Zuniga, Gerardo A. ^{[1, 2, 4]} ; Ribeiro, Joao A. ^{[1, 3]} ; Chavez-Pacheco, Sair M. ^[1]

Affiliation

^[1] Univ Sao Paulo, Inst Ciencias Biomed, Dept Microbiol, Ave Prof Lineu Prestes 1374, BR-05508000 Sao Paulo, SP - Brazil

^[2] Univ Estadual Paulista, Inst Biociencias Letras & Ciencias Exatas IBILCE, Rua Cristovao Colombo 2265, BR-15054000 Sao Paulo - Brazil

^[3] Univ Estadual Campinas, Programa Posgrad Biociencias & Tecnol Prod Bioat, Inst Biol, CPG IB UNICAMP, Rua Monteiro Lobato 255, Cidade Univ, BR-13083862 Campinas, SP - Brazil

^[4] Univ Valle, Fac Salud Escuela Ciencias Basicas, Dept Microbiol, Calle 4B 36-00, Cali, Valle - Colombia

• Document type: Review article
• Source: Future Medicinal Chemistry; v. 10, n. 8, p. 935-959, APR 2018.
• Web of Science Citations: 5

Abstract

Folate pathway is a key target for the development of new drugs against infectious diseases since the discovery of sulfa drugs and trimethoprim. The knowledge about this pathway has increased in the last years and the catalytic mechanism and structures of all enzymes of the pathway are fairly understood. In addition, differences among enzymes from prokaryotes and eukaryotes could be used for the design of specific inhibitors. In this review, we show a panorama of progress that has been achieved within the folate pathway obtained in the last years. We explored the structure and mechanism of enzymes, several genetic features, strategies, and approaches used in the design of new inhibitors that have been used as targets in pathogen chemotherapy. (AU)

• FAPESP's process: 15/09188-8 - Biosynthesis of polyether and aminoglycoside antibiotics: structural investigation of unusual enzymes or with synthetic biology applicability
• Grantee: Marcio Vinicius Bertacine Dias
• Support Opportunities: Regular Research Grants
• FAPESP's process: 13/15906-5 - Fragment based drug discovery (FBDD) applied to two enzymes of folate biosynthetic pathway from Mycobacterium tuberculosis
• Grantee: João Augusto Ribeiro
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 10/15971-3 - Structural characterization of enzymes from antibiotic biosynthetic pathways with biotechnological interest
• Grantee: Marcio Vinicius Bertacine Dias
• Support Opportunities: Research Grants - Young Investigators Grants