Isolation, structure and biological activity of phomafungin, a cyclic lipodepsipeptide from a widespread tropical Phoma sp.
We isolated a cyclic lipodepsipeptide, phomafungin, from a Phoma sp. The distinct antifungal activity of phomafungin in the crude extract was initially discovered by mechanistic profiling in the Candida albicans fitness test. The purified compound contains a 28 member ring consisting of eight amino acids and a beta-hydroxy-gamma-methyl-hexadecanoic acid, and displays a broad spectrum of antifungal activity against Candida spp., Aspergillus fumigatus and Trichophyton mentagrophytes with MIC of 2-8 microg/ml, and toxicity to mice at 25 mg/kg. The linear peptide derived from opening of the lactone ring was devoid of antifungal activity as well as toxicity. Phomafungin has been identified in a number of Phoma spp. collected from Africa and the Indian and Pacific Ocean islands.
Herath
Kithsiri
K
Natural Products Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA.
Harris
Guy
G
Jayasuriya
Hiranthi
H
Zink
Deborah
D
Smith
Scott
S
Vicente
Francisca
F
Bills
Gerald
G
Collado
Javier
J
González
Antonio
A
Jiang
Bo
B
Kahn
Jennifer Nielsen
JN
Galuska
Stefan
S
Giacobbe
Robert
R
Abruzzo
George
G
Hickey
Emily
E
Liberator
Paul
P
Xu
Deming
D
Roemer
Terry
T
Singh
Sheo B
SB
D000595:Amino Acid Sequence; D000818:Animals; D000935:Antifungal Agents / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D001203:Ascomycota / Q000737:chemistry*; D001232:Aspergillus fumigatus / Q000187:drug effects; D047630:Depsipeptides / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D055666:Lipopeptides / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D051379:Mice; D014249:Trichophyton / Q000187:drug effects
D000935:Antifungal Agents; D047630:Depsipeptides; D055666:Lipopeptides; C539861:phomafungin