A non-immunosuppressive FK506 analogue with neuroregenerative activity produced from a genetically engineered Streptomyces strain

Pramod B. Shinde; Yeon Hee Ban; Jae Yeon Hwang; Yumi Cho; Yi Ahn Chen; Eunji Cheong; Sang Jip Nam; Ho Jeong Kwon; Yeo Joon Yoon

doi:10.1039/c4ra11907j

A non-immunosuppressive FK506 analogue with neuroregenerative activity produced from a genetically engineered Streptomyces strain

Pramod B. Shinde, Yeon Hee Ban, Jae Yeon Hwang, Yumi Cho, Yi Ahn Chen, Eunji Cheong, Sang Jip Nam, Ho Jeong Kwon, Yeo Joon Yoon

Department of Chemistry & Nanoscience

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

Abstract

FK506 exhibits neuroprotective and neuroregenerative activities in addition to its clinically important immunosuppressant properties. The macrolide ring of FK506 is biosynthesized by a hybrid polyketide synthase/nonribosomal peptide synthetase system and is further modified via C-9 oxidation by FkbD and 31-O-methylation by FkbM. A new FK506 analogue, 9-deoxo-prolyl-FK506 (1), was isolated from the fkbD deletion mutant of Streptomyces sp. KCTC11604BP, and its biological activities were evaluated. The in vitro immunosuppressive activity was significantly reduced, but in vitro neurite outgrowth activity similar to FK506 was maintained. These results demonstrate the potential of pathway engineering for the modification of structurally complex natural products, such as FK506, to create improved biological agents.

Original language	English
Pages (from-to)	6823-6828
Number of pages	6
Journal	RSC Advances
Volume	5
Issue number	9
DOIs	https://doi.org/10.1039/c4ra11907j
State	Published - 2015

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© The Royal Society of Chemistry 2015.

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abstract = "FK506 exhibits neuroprotective and neuroregenerative activities in addition to its clinically important immunosuppressant properties. The macrolide ring of FK506 is biosynthesized by a hybrid polyketide synthase/nonribosomal peptide synthetase system and is further modified via C-9 oxidation by FkbD and 31-O-methylation by FkbM. A new FK506 analogue, 9-deoxo-prolyl-FK506 (1), was isolated from the fkbD deletion mutant of Streptomyces sp. KCTC11604BP, and its biological activities were evaluated. The in vitro immunosuppressive activity was significantly reduced, but in vitro neurite outgrowth activity similar to FK506 was maintained. These results demonstrate the potential of pathway engineering for the modification of structurally complex natural products, such as FK506, to create improved biological agents.",

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AU - Shinde, Pramod B.

AU - Ban, Yeon Hee

AU - Hwang, Jae Yeon

AU - Cho, Yumi

AU - Chen, Yi Ahn

AU - Cheong, Eunji

AU - Nam, Sang Jip

AU - Kwon, Ho Jeong

AU - Yoon, Yeo Joon

PY - 2015

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AB - FK506 exhibits neuroprotective and neuroregenerative activities in addition to its clinically important immunosuppressant properties. The macrolide ring of FK506 is biosynthesized by a hybrid polyketide synthase/nonribosomal peptide synthetase system and is further modified via C-9 oxidation by FkbD and 31-O-methylation by FkbM. A new FK506 analogue, 9-deoxo-prolyl-FK506 (1), was isolated from the fkbD deletion mutant of Streptomyces sp. KCTC11604BP, and its biological activities were evaluated. The in vitro immunosuppressive activity was significantly reduced, but in vitro neurite outgrowth activity similar to FK506 was maintained. These results demonstrate the potential of pathway engineering for the modification of structurally complex natural products, such as FK506, to create improved biological agents.

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A non-immunosuppressive FK506 analogue with neuroregenerative activity produced from a genetically engineered Streptomyces strain

Abstract

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