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Biosynthesis of novel carotenoid families based on unnatural carbon backbones: A model for diversification of natural product pathways

Tobias, Alexander V. and Arnold, Frances H. (2006) Biosynthesis of novel carotenoid families based on unnatural carbon backbones: A model for diversification of natural product pathways. Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids, 1761 (2). pp. 235-46. ISSN 1388-1981. doi:10.1016/j.bbalip.2006.01.003. https://resolver.caltech.edu/CaltechAUTHORS:20170408-160618170

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Abstract

We show that the C_(40) carotenoid desaturase CrtI from Pantoea ananatis (Erwinia uredovora) is capable of desaturating unnaturally long C_(45) and C_(50) carotenoid backbones in recombinant E. coli. Desaturation step number in these pathways is not very specific, and at least ten new C_(45) and C_(50) carotenoids were synthesized. We also present evidence for a novel asymmetric C_(40) backbone formed by the condensation of farnesyl diphosphate (C_(15)PP) with farnesylgeranyl diphosphate (C_(25)PP), and the subsequent desaturation of this backbone by CrtI in an atypical manner. Under some conditions, the C_(40), C_(45), and C_(50) carotenoid backbones synthesized in E. coli were monohydroxylated; their desaturation by CrtI in vitro led to yet more novel carotenoids. Challenging CrtI with larger-than-natural substrates in vivo has allowed us to show that this enzyme regulates desaturation step number by sensing the end groups of its substrate. Analysis of the mechanisms by which chemical diversity is generated and propagated through the nascent pathways provides insight into how natural product diversification occurs in nature.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1016/j.bbalip.2006.01.003DOIArticle
ORCID:
AuthorORCID
Arnold, Frances H.0000-0002-4027-364X
Additional Information: Received 4 November 2005, Revised 3 January 2006, Accepted 4 January 2006, Available online 30 January 2006. A. Tobias acknowledges support from a Natural Sciences and Engineering Research Council of Canada Postgraduate Scholarship. This work was supported by grant BES-0118565 from the U.S. National Science Foundation. We thank Mona Shahgholi and Nathan Dalleska for valuable assistance with mass spectrometry. We are also grateful to Gerhard Sandmann and George Britton for their technical advice, and to Shinichi Takaichi for providing assistance with the naming of the novel carotenoids.
Funders:
Funding AgencyGrant Number
Natural Sciences and Engineering Research Council of Canada (NSERC)UNSPECIFIED
NSFBES-0118565
Subject Keywords:Molecular evolution; Carotenoid biosynthetic pathway
Issue or Number:2
DOI:10.1016/j.bbalip.2006.01.003
Record Number:CaltechAUTHORS:20170408-160618170
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20170408-160618170
Official Citation:Alexander V. Tobias, Frances H. Arnold, Biosynthesis of novel carotenoid families based on unnatural carbon backbones: A model for diversification of natural product pathways, Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, Volume 1761, Issue 2, February 2006, Pages 235-246, ISSN 1388-1981, https://doi.org/10.1016/j.bbalip.2006.01.003. (http://www.sciencedirect.com/science/article/pii/S1388198106000035)
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:76127
Collection:CaltechAUTHORS
Deposited By: 1Science Import
Deposited On:21 Jun 2017 22:11
Last Modified:15 Nov 2021 16:57

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