Maramycin, a Cytotoxic Isoquinolinequinone Terpenoid Produced through Heterologous Expression of a Bifunctional Indole Prenyltransferase/Tryptophan Indole-Lyase in S. albidoflavus
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Maramycin, a Cytotoxic Isoquinolinequinone Terpenoid Produced through Heterologous Expression of a Bifunctional Indole Prenyltransferase/Tryptophan Indole-Lyase in S. albidoflavus. / Maleckis, Matiss; Wibowo, Mario; Williams, Sam E.; Gotfredsen, Charlotte H.; Sigrist, Renata; Souza, Luciano D.O.; Cowled, Michael S.; Charusanti, Pep; Gren, Tetiana; Saha, Subhasish; Moreira, José M.A.; Weber, Tilmann; Ding, Ling.
In: ACS chemical biology, Vol. 19, No. 6, 2024, p. 1303–1310.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Maramycin, a Cytotoxic Isoquinolinequinone Terpenoid Produced through Heterologous Expression of a Bifunctional Indole Prenyltransferase/Tryptophan Indole-Lyase in S. albidoflavus
AU - Maleckis, Matiss
AU - Wibowo, Mario
AU - Williams, Sam E.
AU - Gotfredsen, Charlotte H.
AU - Sigrist, Renata
AU - Souza, Luciano D.O.
AU - Cowled, Michael S.
AU - Charusanti, Pep
AU - Gren, Tetiana
AU - Saha, Subhasish
AU - Moreira, José M.A.
AU - Weber, Tilmann
AU - Ding, Ling
N1 - Publisher Copyright: © 2024 American Chemical Society.
PY - 2024
Y1 - 2024
N2 - Isoquinolinequinones represent an important family of natural alkaloids with profound biological activities. Heterologous expression of a rare bifunctional indole prenyltransferase/tryptophan indole-lyase enzyme from Streptomyces mirabilis P8-A2 in S. albidoflavus J1074 led to the activation of a putative isoquinolinequinone biosynthetic gene cluster and production of a novel isoquinolinequinone alkaloid, named maramycin (1). The structure of maramycin was determined by analysis of spectroscopic (1D/2D NMR) and MS spectrometric data. The prevalence of this bifunctional biosynthetic enzyme was explored and found to be a recent evolutionary event with only a few representatives in nature. Maramycin exhibited moderate cytotoxicity against human prostate cancer cell lines, LNCaP and C4-2B. The discovery of maramycin (1) enriched the chemical diversity of natural isoquinolinequinones and also provided new insights into crosstalk between the host biosynthetic genes and the heterologous biosynthetic genes in generating new chemical scaffolds.
AB - Isoquinolinequinones represent an important family of natural alkaloids with profound biological activities. Heterologous expression of a rare bifunctional indole prenyltransferase/tryptophan indole-lyase enzyme from Streptomyces mirabilis P8-A2 in S. albidoflavus J1074 led to the activation of a putative isoquinolinequinone biosynthetic gene cluster and production of a novel isoquinolinequinone alkaloid, named maramycin (1). The structure of maramycin was determined by analysis of spectroscopic (1D/2D NMR) and MS spectrometric data. The prevalence of this bifunctional biosynthetic enzyme was explored and found to be a recent evolutionary event with only a few representatives in nature. Maramycin exhibited moderate cytotoxicity against human prostate cancer cell lines, LNCaP and C4-2B. The discovery of maramycin (1) enriched the chemical diversity of natural isoquinolinequinones and also provided new insights into crosstalk between the host biosynthetic genes and the heterologous biosynthetic genes in generating new chemical scaffolds.
U2 - 10.1021/acschembio.4c00121
DO - 10.1021/acschembio.4c00121
M3 - Journal article
C2 - 38743035
AN - SCOPUS:85193541869
VL - 19
SP - 1303
EP - 1310
JO - A C S Chemical Biology
JF - A C S Chemical Biology
SN - 1554-8929
IS - 6
ER -
ID: 393775108