A comprehensive genomic and growth proteomic analysis of antitumor lipopeptide bacillomycin Lb biosynthesis in Bacillus amyloliquefaciens X030

Lu, Jiao Yang; Zhou, Kexuan; Huang, Wei Tao; Zhou, Pengji; Yang, Shuqing; Zhao, Xiaoli; Xie, Junyan; Xia, Liqiu; Ding, Xuezhi

doi:10.1007/s00253-019-10019-6

Genomics, transcriptomics, proteomics
Published: 27 July 2019

A comprehensive genomic and growth proteomic analysis of antitumor lipopeptide bacillomycin Lb biosynthesis in Bacillus amyloliquefaciens X030

Jiao Yang Lu¹,
Kexuan Zhou¹,
Wei Tao Huang¹,
Pengji Zhou¹,
Shuqing Yang¹,
Xiaoli Zhao¹,
Junyan Xie¹,
Liqiu Xia¹ &
Xuezhi Ding ORCID: orcid.org/0000-0001-6784-4978¹

Applied Microbiology and Biotechnology volume 103, pages 7647–7662 (2019)Cite this article

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Abstract

Lipopeptides (such as iturin, fengycin, and surfactin) from Bacillus possess antibacterial, antifungal, and antiviral activities and have important application in agriculture and pharmaceuticals. Although unremitting efforts have been devoted to improve lipopeptide production by designing gene regulatory circuits or optimizing fermentation process, little attention has been paid to utilizing multi-omics for systematically mining core genes and proteins during the bacterial growth cycle. Here, lipopeptide bacillomycin Lb from new Bacillus amyloliquefaciens X030 was isolated and first found to have anticancer activity in various cancer cells (such as SMMC-7721 and MDA-MB-231). A comprehensive genomic and growth proteomic analysis of X030 revealed bacillomycin Lb biosynthetic gene cluster, key enzymes and potential regulatory proteins (PerR, PhoP, CcpA, and CsfB), and novel links between primary metabolism and bacillomycin Lb production in X030. The antitumor activity of the fermentation supernatant supplemented with amino acids (such as glutamic acid) and sucrose was significantly increased, verifying the role of key metabolic switches in the metabolic regulatory network. Quantitative real-time PCR analysis confirmed that 7 differential expressed genes exhibited a positive correlation between changes at transcriptional and translational levels. The study not only will stimulate the deeper and wider antitumor study of lipopeptides but also provide a comprehensive database, which promotes an in-depth analysis of pathways and networks for complex events in lipopeptide biosynthesis and regulation and gives great help in improving the yield of bacillomycin Lb (media optimization, genetic modification, or pathway engineering).

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Funding

This work was financially supported by the National key Research and Development program of China (2017YFD0201201), the National Natural Science Foundation of China (31370116), and the Cooperative Innovation Center of Engineering and New Products for Developmental Biology of Hunan Province (20134486).

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State Key Laboratory of Developmental Biology of Freshwater Fish, Hunan Provincial Key Laboratory of Microbial Molecular Biology, College of Life Science, Hunan Normal University, Changsha, 410081, People’s Republic of China
Jiao Yang Lu, Kexuan Zhou, Wei Tao Huang, Pengji Zhou, Shuqing Yang, Xiaoli Zhao, Junyan Xie, Liqiu Xia & Xuezhi Ding

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Jiao Yang Lu
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Kexuan Zhou
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Wei Tao Huang
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Pengji Zhou
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Shuqing Yang
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Xiaoli Zhao
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Junyan Xie
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Liqiu Xia
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Xuezhi Ding
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Correspondence to Xuezhi Ding.

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Lu, J.Y., Zhou, K., Huang, W.T. et al. A comprehensive genomic and growth proteomic analysis of antitumor lipopeptide bacillomycin Lb biosynthesis in Bacillus amyloliquefaciens X030. Appl Microbiol Biotechnol 103, 7647–7662 (2019). https://doi.org/10.1007/s00253-019-10019-6

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Received: 21 May 2019
Revised: 05 July 2019
Accepted: 09 July 2019
Published: 27 July 2019
Issue Date: September 2019
DOI: https://doi.org/10.1007/s00253-019-10019-6

Keywords

Genomics
Growth proteomics
Bacillomycin Lb
Lipopeptide
Anticancer