NDLI: Polyketide synthase chemistry does not direct biosynthetic divergence between 9- and 10-membered enediynes

Content Provider	PubMed Central
Author	Horsman, Geoff P. Chen, Yihua Thorson, Jon S. Shen, Ben
Abstract	Enediynes are potent antitumor antibiotics that are classified as 9- or 10-membered according to the size of the enediyne core structure. However, almost nothing is known about enediyne core biosynthesis, and the determinants of 9- versus 10-membered enediyne core biosynthetic divergence remain elusive. Previous work identified enediyne-specific polyketide synthases (PKSEs) that can be phylogenetically distinguished as being involved in 9- versus 10-membered enediyne biosynthesis, suggesting that biosynthetic divergence might originate from differing PKSE chemistries. Recent in vitro studies have identified several compounds produced by the PKSE and associated thioesterase (TE), but condition-dependent product profiles make it difficult to ascertain a true catalytic difference between 9- and 10-membered PKSE-TE systems. Here we report that PKSE chemistry does not direct 9- versus 10-membered enediyne core biosynthetic divergence as revealed by comparing the products from three 9-membered and two 10-membered PKSE-TE systems under identical conditions using robust in vivo assays. Three independent experiments support a common catalytic function for 9- and 10-membered PKSEs by the production of a heptaene metabolite from: (i) all five cognate PKSE-TE pairs in Escherichia coli; (ii) the C-1027 and calicheamicin cognate PKSE-TEs in Streptomyces lividans K4-114; and (iii) selected native producers of both 9- and 10-membered enediynes. Furthermore, PKSEs and TEs from different 9- and 10-membered enediyne biosynthetic machineries are freely interchangeable, revealing that 9- versus 10-membered enediyne core biosynthetic divergence occurs beyond the PKSE-TE level. These findings establish a starting point for determining the origins of this biosynthetic divergence.
Related Links	http://dx.doi.org/10.1073/pnas.1003442107
Ending Page	11335
Page Count	5
Starting Page	11331
File Format	PDF
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	25
Volume Number	107
Language	English
Publisher	National Academy of Sciences
Publisher Date	2010-06-22
Access Restriction	Open
Rights Holder	National Academy of Sciences
Subject Keyword	General Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Identification of a bioactive 51-membered macrolide complex by activation of a silent polyketide synthase in Streptomyces ambofaciens

Direct evidence that the rifamycin polyketide synthase assembles polyketide chains processively

Type I polyketide synthase requiring a discrete acyltransferase for polyketide biosynthesis

Structure of a modular polyketide synthase

Structural basis for biosynthetic programming of fungal aromatic polyketide cyclization

C-S bond cleavage by a polyketide synthase domain

Atlas of nonribosomal peptide and polyketide biosynthetic pathways reveals common occurrence of nonmodular enzymes

The Biosynthetic Gene Cluster for the 26-Membered Ring Polyene Macrolide Pimaricin A NEW POLYKETIDE SYNTHASE ORGANIZATION ENCODED BY TWO SUBCLUSTERS SEPARATED BY FUNCTIONALIZATION GENES

A polyketide macrolactone synthase from the filamentous fungus Gibberella zeae

Polyketide synthase chemistry does not direct biosynthetic divergence between 9- and 10-membered enediynes

Similar Documents

Identification of a bioactive 51-membered macrolide complex by activation of a silent polyketide synthase in Streptomyces ambofaciens

Direct evidence that the rifamycin polyketide synthase assembles polyketide chains processively

Type I polyketide synthase requiring a discrete acyltransferase for polyketide biosynthesis

Structure of a modular polyketide synthase

Structural basis for biosynthetic programming of fungal aromatic polyketide cyclization

C-S bond cleavage by a polyketide synthase domain

Atlas of nonribosomal peptide and polyketide biosynthetic pathways reveals common occurrence of nonmodular enzymes

The Biosynthetic Gene Cluster for the 26-Membered Ring Polyene Macrolide Pimaricin A NEW POLYKETIDE SYNTHASE ORGANIZATION ENCODED BY TWO SUBCLUSTERS SEPARATED BY FUNCTIONALIZATION GENES

A polyketide macrolactone synthase from the filamentous fungus Gibberella zeae

Polyketide synthase chemistry does not direct biosynthetic divergence between 9- and 10-membered enediynes