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Applied Microbiology and Biotechnology

, Volume 103, Issue 18, pp 7647–7662 | Cite as

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

  • Jiao Yang Lu
  • Kexuan Zhou
  • Wei Tao Huang
  • Pengji Zhou
  • Shuqing Yang
  • Xiaoli Zhao
  • Junyan Xie
  • Liqiu Xia
  • Xuezhi DingEmail author
Genomics, transcriptomics, proteomics

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).

Keywords

Genomics Growth proteomics Bacillomycin Lb Lipopeptide Anticancer 

Notes

Funding information

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).

Compliance with ethical standards

This study did not involve any research involving human participants or animals.

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

253_2019_10019_MOESM1_ESM.pdf (1.1 mb)
ESM 1 (PDF 1173 kb)
253_2019_10019_MOESM2_ESM.xlsx (3 mb)
ESM 2 (XLSX 3053 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.State Key Laboratory of Developmental Biology of Freshwater Fish, Hunan Provincial Key Laboratory of Microbial Molecular Biology, College of Life ScienceHunan Normal UniversityChangshaPeople’s Republic of China

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