TY - JOUR
T1 - Discovery and Characterization of Epemicins A and B, New 30-Membered Macrolides from Kutzneria sp. CA-103260
AU - Kontou, Eftychia Eva
AU - Gren, Tetiana
AU - Ortiz-López, Francisco Javier
AU - Thomsen, Emil
AU - Oves-Costales, Daniel
AU - Díaz, Caridad
AU - de la Cruz, Mercedes
AU - Jiang, Xinglin
AU - Jørgensen, Tue Sparholt
AU - Blin, Kai
AU - Charusanti, Pep
AU - Reyes, Fernando
AU - Genilloud, Olga
AU - Weber, Tilmann
PY - 2021
Y1 - 2021
N2 - Actinobacteria have been a rich source of novel, structurally complex natural products for many decades. Although the largest genus is Streptomyces, from which the majority of antibiotics in current and past clinical use were originally isolated, other less common genera also have the potential to produce a wealth of novel secondary metabolites. One example is the Kutzneria genus, which currently contains only five reported species. One of these species is Kutzneria albida DSM 43870T, which has 46 predicted biosynthetic gene clusters and is known to produce the macrolide antibiotic aculeximycin. Here, we report the isolation and structural characterization of two novel 30-membered glycosylated macrolides, epemicins A and B, that are structurally related to aculeximycin, from a rare Kutzneria sp. The absolute configuration for all chiral centers in the two compounds is proposed based on extensive 1D and 2D NMR studies and bioinformatics analysis of the gene cluster. Through heterologous expression and genetic inactivation, we have confirmed the link between the biosynthetic gene cluster and the new molecules. These findings show the potential of rare Actinobacteria to produce new, structurally diverse metabolites. Furthermore, the gene inactivation represents the first published report to genetically manipulate a representative of the Kutzneria genus.
AB - Actinobacteria have been a rich source of novel, structurally complex natural products for many decades. Although the largest genus is Streptomyces, from which the majority of antibiotics in current and past clinical use were originally isolated, other less common genera also have the potential to produce a wealth of novel secondary metabolites. One example is the Kutzneria genus, which currently contains only five reported species. One of these species is Kutzneria albida DSM 43870T, which has 46 predicted biosynthetic gene clusters and is known to produce the macrolide antibiotic aculeximycin. Here, we report the isolation and structural characterization of two novel 30-membered glycosylated macrolides, epemicins A and B, that are structurally related to aculeximycin, from a rare Kutzneria sp. The absolute configuration for all chiral centers in the two compounds is proposed based on extensive 1D and 2D NMR studies and bioinformatics analysis of the gene cluster. Through heterologous expression and genetic inactivation, we have confirmed the link between the biosynthetic gene cluster and the new molecules. These findings show the potential of rare Actinobacteria to produce new, structurally diverse metabolites. Furthermore, the gene inactivation represents the first published report to genetically manipulate a representative of the Kutzneria genus.
U2 - 10.1021/acschembio.1c00318
DO - 10.1021/acschembio.1c00318
M3 - Journal article
C2 - 34279911
SN - 1554-8929
VL - 16
SP - 1456
EP - 1468
JO - ACS chemical biology
JF - ACS chemical biology
IS - 8
ER -