TY - JOUR
T1 - Revitalizing antifolates through understanding mechanisms that govern susceptibility and resistance
AU - Kordus, Shannon Lynn
AU - Baughn, Anthony David
N1 - Publisher Copyright:
© 2019 The Royal Society of Chemistry.
PY - 2019
Y1 - 2019
N2 - In prokaryotes and eukaryotes, folate (vitamin B9) is an essential metabolic cofactor required for all actively growing cells. Specifically, folate serves as a one-carbon carrier in the synthesis of amino acids (such as methionine, serine, and glycine), N-formylmethionyl-tRNA, coenzyme A, purines and thymidine. Many microbes are unable to acquire folates from their environment and rely on de novo folate biosynthesis. In contrast, mammals lack the de novo folate biosynthesis pathway and must obtain folate from commensal microbiota or the environment using proton-coupled folate transporters. The essentiality and dichotomy between mammalian and bacterial folate biosynthesis and utilization pathways make it an ideal drug target for the development of antimicrobial agents and cancer chemotherapeutics. In this minireview, we discuss general aspects of folate biosynthesis and the underlying mechanisms that govern susceptibility and resistance of organisms to antifolate drugs.
AB - In prokaryotes and eukaryotes, folate (vitamin B9) is an essential metabolic cofactor required for all actively growing cells. Specifically, folate serves as a one-carbon carrier in the synthesis of amino acids (such as methionine, serine, and glycine), N-formylmethionyl-tRNA, coenzyme A, purines and thymidine. Many microbes are unable to acquire folates from their environment and rely on de novo folate biosynthesis. In contrast, mammals lack the de novo folate biosynthesis pathway and must obtain folate from commensal microbiota or the environment using proton-coupled folate transporters. The essentiality and dichotomy between mammalian and bacterial folate biosynthesis and utilization pathways make it an ideal drug target for the development of antimicrobial agents and cancer chemotherapeutics. In this minireview, we discuss general aspects of folate biosynthesis and the underlying mechanisms that govern susceptibility and resistance of organisms to antifolate drugs.
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U2 - 10.1039/c9md00078j
DO - 10.1039/c9md00078j
M3 - Review article
C2 - 31303985
AN - SCOPUS:85067692553
SN - 2040-2503
VL - 10
SP - 880
EP - 895
JO - MedChemComm
JF - MedChemComm
IS - 6
ER -