Applied Microbiology and Biotechnology

, Volume 104, Issue 3, pp 953–965 | Cite as

Principle and potential applications of the non-classical protein secretory pathway in bacteria

  • Qian Kang
  • Dawei ZhangEmail author


In addition to the extracellular proteins secreted by known secretory pathways, a number of cytoplasmic proteins without predicable or known signal sequences or secretory motifs have been found in the extracellular milieu, and were consequently classified as non-classically secreted proteins. Non-classical protein secretion is considered to be a general, conserved cellular phenomenon in both eukaryotes and prokaryotes. There are several research hotspots on the non-classical protein secretory pathway, and the most important two of them are the recognition principle of substrate proteins and possible secretory mechanisms. To date, researchers have made some progress in understanding the characteristics of these proteins. For example, it was discovered that many non-classically secreted proteins exist and are secreted in multimeric form. Some of these proteins prefer to be clustered and exported at the poles and the septum of the cell. The majority of these proteins play different functions when they are in the intra- and extracellular environments, and several of their functions are related to survival and pathogenicity. Furthermore, non-classically secreted proteins can be used as leading proteins to guide a POI (protein of interest) out of the cells, which provides a novel strategy for protein secretion with potential applications in the industry. Summarizing these findings, this review emphasizes the hot spots related to non-classically secreted proteins in bacteria, lists the most important hypotheses on the selection and secretion mechanisms of non-classically secreted proteins, and put forward their potential applications.


Non-classical secretion pathway Secretion mechanism Protein secretion Signal-less proteins 



The authors wish to express their gratitude for the great support received from the funding agencies.

Availability of data and materials

This is a review article without original data.

Authors’ contributions

QK and DZ conceived the review; QK and DZ wrote the manuscript.

Funding information

This work was supported by the National Key R&D Program of China (2018YFA0900302, 2018YFD0901001), the National Natural Science Foundation of China (NSFC 31800086), the Tianjin Science Fund for Distinguished Young Scholars (17JCJQJC45300), and the Science and Technology Service Network (STS) Initiative of the Chinese Academy of Sciences (CAS) (KFJ-STS-ZDTP-065).

Compliance with ethical standards

Ethics approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Conflict of interest

The authors declare that they have no conflict of interest.


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

Authors and Affiliations

  1. 1.Tianjin Institute of Industrial BiotechnologyChinese Academy of SciencesTianjinPeople’s Republic of China
  2. 2.Key Laboratory of Systems Microbial BiotechnologyChinese Academy of SciencesTianjinPeople’s Republic of China
  3. 3.University of Chinese Academy of SciencesBeijingChina

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