Genetic dissection of the polyoxin building block-carbamoylpolyoxamic acid biosynthesis revealing the “pathway redundancy” in metabolic networks

Microbial Cell Factories

Research

Changchun Wang¹  Wenqing Chen²  Zixin Deng³  Tingting Huang⁴  Lipeng Zhai⁴  Daofeng Dai⁴ 

[1] Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education, and School of Pharmaceutical Sciences, Wuhan University, 185 East Lake Road, P.R., 430071, Wuhan, China;Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education, and School of Pharmaceutical Sciences, Wuhan University, 185 East Lake Road, P.R., 430071, Wuhan, China;State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, 200237, Shanghai, China;State Key Laboratory of Microbial Metabolism, and School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, 200030, Shanghai, China;Department of Chemical and Biomolecular Engineering, University of California, 90095, Los Angeles, California, USA;Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education, and School of Pharmaceutical Sciences, Wuhan University, 185 East Lake Road, P.R., 430071, Wuhan, China;State Key Laboratory of Microbial Metabolism, and School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, 200030, Shanghai, China;State Key Laboratory of Microbial Metabolism, and School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, 200030, Shanghai, China;

关键词: Polyoxin;    Building block;    Carbamoylpolyoxamic acid;    Pathway redundancy;    Metabolic networks;   

DOI  :  10.1186/1475-2859-12-121

 received in 2013-09-24, accepted in 2013-11-24,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundPolyoxin, a peptidyl nucleoside antibiotic, consists of three building blocks including a nucleoside skeleton, polyoximic acid (POIA), and carbamoylpolyoxamic acid (CPOAA), however, little is known about the “pathway redundancy” of the metabolic networks directing the CPOAA biosynthesis in the cell factories of the polyoxin producer.ResultsHere we report the genetic characterization of CPOAA biosynthesis with revealing a “pathway redundancy” in metabolic networks. Independent mutation of the four genes (polL-N and polP) directly resulted in the accumulation of polyoxin I, suggesting their positive roles for CPOAA biosynthesis. Moreover, the individual mutant of polN and polP also partially retains polyoxin production, suggesting the existence of the alternative homologs substituting their functional roles.ConclusionsIt is unveiled that argA and argB in L-arginine biosynthetic pathway contributed to the “pathway redundancy”, more interestingly, argB in S. cacaoi is indispensible for both polyoxin production and L-arginine biosynthesis. These data should provide an example for the research on the “pathway redundancy” in metabolic networks, and lay a solid foundation for targeted enhancement of polyoxin production with synthetic biology strategies.

【 授权许可】

Unknown   
© Chen et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.