TY - JOUR
T1 - Leinamycin Biosynthesis Revealing Unprecedented Architectural Complexity for a Hybrid Polyketide Synthase and Nonribosomal Peptide Synthetase
AU - Tang, Gong Li
AU - Cheng, Yi Qiang
AU - Shen, Ben
N1 - Funding Information:
We thank Kyowa Hakko Kogyo Co. Ltd., Tokyo, Japan, for an authentic sample of leinamycin, the wild-type S. atroolivaceus S-140 strain, and assistance in sequencing the lnm gene cluster. This work is supported in part by University of California BioSTAR Program Grant Bio99-10045 and Kosan Biosciences, Inc. (Hayward, CA). B.S. is a recipient of National Science Foundation CAREER Award MCB9733938 and National Institutes of Health Independent Scientist Award AI51689.
PY - 2004/1
Y1 - 2004/1
N2 - A 135,638 bp DNA region that encompasses the leinamycin (LNM) biosynthetic gene cluster was sequenced from Streptomyces atroolivaceus S-140. The boundaries of the lnm cluster were defined by systematic inactivation of open reading frames within the sequenced region. The lnm cluster spans 61.3 kb of DNA and consists of 27 genes encoding nonribosomal peptide synthetase (NRPS), polyketide synthase (PKS), hybrid NRPS-PKS, resistance, regulatory, and tailoring enzymes, as well as proteins of unknown function. A model for LNM biosynthesis is proposed, central to which is the LNM hybrid NRPS-PKS megasynthetase consisting of discrete (LnmQ and LnmP) and modular (LnmI) NRPS, acyltransferase-less PKS (LnmG, LnmI, and LnmJ), and PKS modules with unusual domain organization. These studies unveil an unprecedented architectural complexity for the LNM hybrid NRPS-PKS megasynthetase and set the stage to investigate the molecular basis for LNM biosynthesis.
AB - A 135,638 bp DNA region that encompasses the leinamycin (LNM) biosynthetic gene cluster was sequenced from Streptomyces atroolivaceus S-140. The boundaries of the lnm cluster were defined by systematic inactivation of open reading frames within the sequenced region. The lnm cluster spans 61.3 kb of DNA and consists of 27 genes encoding nonribosomal peptide synthetase (NRPS), polyketide synthase (PKS), hybrid NRPS-PKS, resistance, regulatory, and tailoring enzymes, as well as proteins of unknown function. A model for LNM biosynthesis is proposed, central to which is the LNM hybrid NRPS-PKS megasynthetase consisting of discrete (LnmQ and LnmP) and modular (LnmI) NRPS, acyltransferase-less PKS (LnmG, LnmI, and LnmJ), and PKS modules with unusual domain organization. These studies unveil an unprecedented architectural complexity for the LNM hybrid NRPS-PKS megasynthetase and set the stage to investigate the molecular basis for LNM biosynthesis.
UR - http://www.scopus.com/inward/record.url?scp=1142293995&partnerID=8YFLogxK
U2 - 10.1016/j.chembiol.2003.12.014
DO - 10.1016/j.chembiol.2003.12.014
M3 - Article
C2 - 15112993
AN - SCOPUS:1142293995
SN - 1074-5521
VL - 11
SP - 33
EP - 45
JO - Chemistry and Biology
JF - Chemistry and Biology
IS - 1
ER -