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Microbial natural products, among them a vast diversity of fungal origin, represent a major source for new drug candidates. Focusing on fungal metabolites, our review covers recent advances in the field of biotransformation, heterologous expression, in vivo production approaches, genomics, and the metabolism of unexplored fungal groups as options to generate and identify new compounds or optimize known ones.

2',3'-Epimino analogues of neamine, ribostamycin, and kanamycin B possessing little or no intrinsic antimicrobial activity were designed to enhance the activity of kanamycin A against bacterial strains that elaborate aminoglycoside 3'-phosphotransferases. Routes were devised for their synthesis from the parent antibiotics and the 2'',3''-epimino analogue of kanamycin B also was prepared. None of these analogues was active against phosphotransferase-producing bacteria, although the kanamycin B derivatives showed very weak activity against nonresistant strains. At 8 and 32 microgram/mL, the 2',3'-epimino analogue of neamine produced a small synergistic effect on the activity of kanamycin A against a strain of Escherichia coli that produces aminoglycoside 3'-phosphotransferase II. The N3-(carbobenzyloxy) derivative of this analogue produced a small effect against the same strain, and it, as well as the 2'',3''-epimino analogue of kanamycin B, slightly enhanced the activity of kanamycin A against a strain of Proteus rettgeri that elaborates a similar enzyme.