Epoxinnamide: An Epoxy Cinnamoyl-Containing Nonribosomal Peptide from an Intertidal Mudflat-Derived Streptomyces sp.

Sangwook Kang; Jaeho Han; Sung Chul Jang; Joon Soo An; Ilnam Kang; Yun Kwon; Sang Jip Nam; Sang Hee Shim; Jang Cheon Cho; Sang Kook Lee; Dong Chan Oh

doi:10.3390/md20070455

Epoxinnamide: An Epoxy Cinnamoyl-Containing Nonribosomal Peptide from an Intertidal Mudflat-Derived Streptomyces sp.

Sangwook Kang, Jaeho Han, Sung Chul Jang, Joon Soo An, Ilnam Kang, Yun Kwon, Sang Jip Nam, Sang Hee Shim, Jang Cheon Cho, Sang Kook Lee, Dong Chan Oh

Chemistry & Nanoscience

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

1 Scopus citations

Abstract

Cinnamoyl-containing nonribosomal peptides (CCNPs) form a unique family of actinobacterial secondary metabolites and display various biological activities. A new CCNP named epoxinnamide (1) was discovered from intertidal mudflat-derived Streptomyces sp. OID44. The structure of 1 was determined by the analysis of one-dimensional (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR) data along with a mass spectrum. The absolute configuration of 1 was assigned by the combination of advanced Marfey’s method, ³J_HH and rotating-frame overhauser effect spectroscopy (ROESY) analysis, DP4 calculation, and genomic analysis. The putative biosynthetic pathway of epoxinnamide (1) was identified through the whole-genome sequencing of Streptomyces sp. OID44. In particular, the thioesterase domain in the nonribosomal peptide synthetase (NRPS) biosynthetic gene cluster was proposed as a bifunctional enzyme, which catalyzes both epimerization and macrocyclization. Epoxinnamide (1) induced quinone reductase (QR) activity in murine Hepa-1c1c7 cells by 1.6-fold at 5 μM. It also exhibited effective antiangiogenesis activity in human umbilical vein endothelial cells (IC₅₀ = 13.4 μM).

Original language	English
Article number	455
Journal	Marine Drugs
Volume	20
Issue number	7
DOIs	https://doi.org/10.3390/md20070455
State	Published - Jul 2022

Bibliographical note

Funding Information:
Molecular graphics and analyses of proteins performed with UCSF ChimeraX, developed by the Resource for Biocomputing, Visualization, and Informatics at the University of California, San Francisco, with support from National Institutes of Health R01-GM129325 and the Office of Cyber Infrastructure and Computational Biology, National Institute of Allergy and Infectious Diseases.

Funding Information:
This work was supported by the National Research Foundation of Korea grants funded by the Korean Government (Ministry of Science and ICT) (2021R1A4A2001251 and 2020R1A2C2003518).

Publisher Copyright:
© 2022 by the authors.

Keywords

Streptomyces
angiogenesis
bifunctional thioesterase
biosynthetic gene cluster
cinnamoyl-containing nonribosomal peptide
quinone reductase

Access to Document

10.3390/md20070455

Cite this

@article{da7972da270343eb908993bc722d3907,

title = "Epoxinnamide: An Epoxy Cinnamoyl-Containing Nonribosomal Peptide from an Intertidal Mudflat-Derived Streptomyces sp.",

abstract = "Cinnamoyl-containing nonribosomal peptides (CCNPs) form a unique family of actinobacterial secondary metabolites and display various biological activities. A new CCNP named epoxinnamide (1) was discovered from intertidal mudflat-derived Streptomyces sp. OID44. The structure of 1 was determined by the analysis of one-dimensional (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR) data along with a mass spectrum. The absolute configuration of 1 was assigned by the combination of advanced Marfey{\textquoteright}s method, 3JHH and rotating-frame overhauser effect spectroscopy (ROESY) analysis, DP4 calculation, and genomic analysis. The putative biosynthetic pathway of epoxinnamide (1) was identified through the whole-genome sequencing of Streptomyces sp. OID44. In particular, the thioesterase domain in the nonribosomal peptide synthetase (NRPS) biosynthetic gene cluster was proposed as a bifunctional enzyme, which catalyzes both epimerization and macrocyclization. Epoxinnamide (1) induced quinone reductase (QR) activity in murine Hepa-1c1c7 cells by 1.6-fold at 5 μM. It also exhibited effective antiangiogenesis activity in human umbilical vein endothelial cells (IC50 = 13.4 μM).",

keywords = "Streptomyces, angiogenesis, bifunctional thioesterase, biosynthetic gene cluster, cinnamoyl-containing nonribosomal peptide, quinone reductase",

author = "Sangwook Kang and Jaeho Han and Jang, {Sung Chul} and An, {Joon Soo} and Ilnam Kang and Yun Kwon and Nam, {Sang Jip} and Shim, {Sang Hee} and Cho, {Jang Cheon} and Lee, {Sang Kook} and Oh, {Dong Chan}",

note = "Funding Information: Molecular graphics and analyses of proteins performed with UCSF ChimeraX, developed by the Resource for Biocomputing, Visualization, and Informatics at the University of California, San Francisco, with support from National Institutes of Health R01-GM129325 and the Office of Cyber Infrastructure and Computational Biology, National Institute of Allergy and Infectious Diseases. Funding Information: This work was supported by the National Research Foundation of Korea grants funded by the Korean Government (Ministry of Science and ICT) (2021R1A4A2001251 and 2020R1A2C2003518). Publisher Copyright: {\textcopyright} 2022 by the authors.",

year = "2022",

month = jul,

doi = "10.3390/md20070455",

language = "English",

volume = "20",

journal = "Marine Drugs",

issn = "1660-3397",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

number = "7",

}

TY - JOUR

T1 - Epoxinnamide

T2 - An Epoxy Cinnamoyl-Containing Nonribosomal Peptide from an Intertidal Mudflat-Derived Streptomyces sp.

AU - Kang, Sangwook

AU - Han, Jaeho

AU - Jang, Sung Chul

AU - An, Joon Soo

AU - Kang, Ilnam

AU - Kwon, Yun

AU - Nam, Sang Jip

AU - Shim, Sang Hee

AU - Cho, Jang Cheon

AU - Lee, Sang Kook

AU - Oh, Dong Chan

N1 - Funding Information: Molecular graphics and analyses of proteins performed with UCSF ChimeraX, developed by the Resource for Biocomputing, Visualization, and Informatics at the University of California, San Francisco, with support from National Institutes of Health R01-GM129325 and the Office of Cyber Infrastructure and Computational Biology, National Institute of Allergy and Infectious Diseases. Funding Information: This work was supported by the National Research Foundation of Korea grants funded by the Korean Government (Ministry of Science and ICT) (2021R1A4A2001251 and 2020R1A2C2003518). Publisher Copyright: © 2022 by the authors.

PY - 2022/7

Y1 - 2022/7

N2 - Cinnamoyl-containing nonribosomal peptides (CCNPs) form a unique family of actinobacterial secondary metabolites and display various biological activities. A new CCNP named epoxinnamide (1) was discovered from intertidal mudflat-derived Streptomyces sp. OID44. The structure of 1 was determined by the analysis of one-dimensional (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR) data along with a mass spectrum. The absolute configuration of 1 was assigned by the combination of advanced Marfey’s method, 3JHH and rotating-frame overhauser effect spectroscopy (ROESY) analysis, DP4 calculation, and genomic analysis. The putative biosynthetic pathway of epoxinnamide (1) was identified through the whole-genome sequencing of Streptomyces sp. OID44. In particular, the thioesterase domain in the nonribosomal peptide synthetase (NRPS) biosynthetic gene cluster was proposed as a bifunctional enzyme, which catalyzes both epimerization and macrocyclization. Epoxinnamide (1) induced quinone reductase (QR) activity in murine Hepa-1c1c7 cells by 1.6-fold at 5 μM. It also exhibited effective antiangiogenesis activity in human umbilical vein endothelial cells (IC50 = 13.4 μM).

AB - Cinnamoyl-containing nonribosomal peptides (CCNPs) form a unique family of actinobacterial secondary metabolites and display various biological activities. A new CCNP named epoxinnamide (1) was discovered from intertidal mudflat-derived Streptomyces sp. OID44. The structure of 1 was determined by the analysis of one-dimensional (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR) data along with a mass spectrum. The absolute configuration of 1 was assigned by the combination of advanced Marfey’s method, 3JHH and rotating-frame overhauser effect spectroscopy (ROESY) analysis, DP4 calculation, and genomic analysis. The putative biosynthetic pathway of epoxinnamide (1) was identified through the whole-genome sequencing of Streptomyces sp. OID44. In particular, the thioesterase domain in the nonribosomal peptide synthetase (NRPS) biosynthetic gene cluster was proposed as a bifunctional enzyme, which catalyzes both epimerization and macrocyclization. Epoxinnamide (1) induced quinone reductase (QR) activity in murine Hepa-1c1c7 cells by 1.6-fold at 5 μM. It also exhibited effective antiangiogenesis activity in human umbilical vein endothelial cells (IC50 = 13.4 μM).

KW - Streptomyces

KW - angiogenesis

KW - bifunctional thioesterase

KW - biosynthetic gene cluster

KW - cinnamoyl-containing nonribosomal peptide

KW - quinone reductase

UR - http://www.scopus.com/inward/record.url?scp=85135282546&partnerID=8YFLogxK

U2 - 10.3390/md20070455

DO - 10.3390/md20070455

M3 - Article

C2 - 35877748

AN - SCOPUS:85135282546

SN - 1660-3397

VL - 20

JO - Marine Drugs

JF - Marine Drugs

IS - 7

M1 - 455

ER -

Epoxinnamide: An Epoxy Cinnamoyl-Containing Nonribosomal Peptide from an Intertidal Mudflat-Derived Streptomyces sp.

Abstract

Bibliographical note

Keywords

Access to Document

Fingerprint

Cite this