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Rational design for over-production of desirable microbial metabolites by precision engineering

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Antonie van Leeuwenhoek Aims and scope Submit manuscript

Abstract

Microbes represent a valuable source of commercially significant natural products that have improved our quality of life. Precision engineering can be used to precisely identify and specifically modify genes responsible for production of natural products and improve this production or modify the genes creating products that would not otherwise be produced. There have been several success stories concerning the manipulation of regulatory genes, pathways, and genomes to increase the productivity of industrial microbes. This review will focus on the strategies and integrated approaches for precisely deciphering regulatory genes by various modern techniques. The applications of precision engineering in rational strain improvement also shed light on the biology of natural microbial systems.

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Abbreviations

pre-NDA:

pre-New drug application

MFA:

Metabolic flux analysis

SAM:

S-adenosylmethionine

CoA:

Coenzyme A

1,3-PD:

1,3-Propanediol

ALDH:

Aldehyde dehydrogenase

DCA:

Dicarboxylic acid

TCA:

Tricarboxylic acid

HMG-CoA:

3-hydroxy-3-methyl-glutaryl-coenzyme A

ADS:

Amorphadiene synthase

tHMGR:

HMG-CoA reductase

CEF:

control effective flux

PCA:

Principal component analysis

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Acknowledgments

We thank Prof. Arnold Demain for critical reading of the manuscript and helpful discussions. This work was supported in part by grants from National Natural Science Foundation of China (No. 30700015), National 863 project (2006AA09Z402 and 2007AA09Z443), and Key Project of International Cooperation (2007DFB31620). National Key Technology R&D Program 2007BAI26B02, the National Science & Technology Pillar Program (No. 200703295000-02), Important National Science & Technology Specific Projects (No. 2008ZX09401-05), and Science and Technology Planning Project of Guangdong Province, China (No. 2006A50103001). L.Z. was an awardee for Hundred Talents Program.

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Authors and Affiliations

  1. Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, People’s Republic of China

    Hong Gao, Xianlong Zhou, Zhongxuan Gou, Ying Zhuo, Chengzhang Fu, Mei Liu, Fuhang Song, Elizabeth Ashforth & Lixin Zhang

  2. Graduate University of Chinese Academy of Sciences, Beijing, People’s Republic of China

    Ying Zhuo & Chengzhang Fu

Authors
  1. Hong Gao
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  2. Xianlong Zhou
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  3. Zhongxuan Gou
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  4. Ying Zhuo
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  5. Chengzhang Fu
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  6. Mei Liu
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  7. Fuhang Song
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  8. Elizabeth Ashforth
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  9. Lixin Zhang
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Corresponding author

Correspondence to Lixin Zhang.

Additional information

H. Gao, X. Zhou, and Z. Gou contributed equally to this work.

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Gao, H., Zhou, X., Gou, Z. et al. Rational design for over-production of desirable microbial metabolites by precision engineering. Antonie van Leeuwenhoek 98, 151–163 (2010). https://doi.org/10.1007/s10482-010-9442-4

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  • DOI: https://doi.org/10.1007/s10482-010-9442-4

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