TY - JOUR
T1 - Amino-group carrier-protein-mediated secondary metabolite biosynthesis in Streptomyces
AU - Hasebe, Fumihito
AU - Matsuda, Kenichi
AU - Shiraishi, Taro
AU - Futamura, Yushi
AU - Nakano, Takeshi
AU - Tomita, Takeo
AU - Ishigami, Ken
AU - Taka, Hikari
AU - Mineki, Reiko
AU - Fujimura, Tsutomu
AU - Osada, Hiroyuki
AU - Kuzuyama, Tomohisa
AU - Nishiyama, Makoto
N1 - Funding Information:
This work was supported in part by the Japan Society for the Promotion of Science (KAKENHI grant no. 24228001 to M.N.) and the Japan Foundation for Applied Enzymology (M.N.). We thank M. Tanaka (Daiichi Sankyo, Tokyo, Japan) for kindly providing Streptomyces sp. SANK 60404, and M. Kobayasi (Tsukuba University, Tsukuba, Japan) for providing pHS19. srcts-NRK cells were a gift from Y. Uehara (Iwate Medical University, Morioka, Japan). We thank H. Aono, F. Ito, M. Tanaka, and K. Yamamoto for evaluating cytotoxicity and antimicrobial activities, and Y. Kamide for evaluating regulatory activities in plants.
Publisher Copyright:
© 2016 Nature America, Inc. All rights reserved.
PY - 2016/11/1
Y1 - 2016/11/1
N2 - Amino-group carrier proteins (AmCPs) mediate the biosynthesis of lysine and arginine in some bacteria and archaea. Here we demonstrate that an uncharacterized AmCP-mediated biosynthetic system functions to biosynthesize the previously uncharacterized and nonproteinogenic amino acid (2S,6R)-diamino-(5R,7)-dihydroxy-heptanoic acid (DADH) in Streptomyces sp. SANK 60404. DADH is incorporated into a novel peptide metabolite, vazabitide A, featuring an azabicyclo-ring structure, by nonribosomal peptide synthetases and successive modification enzymes in this bacterium. As the AmCP-mediated machinery for DADH biosynthesis is widely distributed in bacteria, further analysis of uncharacterized AmCP-containing gene clusters will lead to the discovery of novel bioactive compounds and novel biosynthetic enzymes.
AB - Amino-group carrier proteins (AmCPs) mediate the biosynthesis of lysine and arginine in some bacteria and archaea. Here we demonstrate that an uncharacterized AmCP-mediated biosynthetic system functions to biosynthesize the previously uncharacterized and nonproteinogenic amino acid (2S,6R)-diamino-(5R,7)-dihydroxy-heptanoic acid (DADH) in Streptomyces sp. SANK 60404. DADH is incorporated into a novel peptide metabolite, vazabitide A, featuring an azabicyclo-ring structure, by nonribosomal peptide synthetases and successive modification enzymes in this bacterium. As the AmCP-mediated machinery for DADH biosynthesis is widely distributed in bacteria, further analysis of uncharacterized AmCP-containing gene clusters will lead to the discovery of novel bioactive compounds and novel biosynthetic enzymes.
UR - http://www.scopus.com/inward/record.url?scp=84988733172&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84988733172&partnerID=8YFLogxK
U2 - 10.1038/nchembio.2181
DO - 10.1038/nchembio.2181
M3 - Article
C2 - 28288097
AN - SCOPUS:84988733172
SN - 1552-4450
VL - 12
SP - 967
EP - 972
JO - Nature Chemical Biology
JF - Nature Chemical Biology
IS - 11
ER -