Heterologous gene expression and secretion in gram-positive bacteria with industrial applications



Rafael P. Mellado

Group Leader



Research summary

The group has traditionally focused its research on the physiological and molecular characterisation of the main protein secretion mechanism (Sec system) of the soil Gram-positive bacteria of the Streptomyces genus, namely S. coelicolor. These are widely used in industry as efficient producers of extracellular hydrolytic enzymes and other compounds of industrial interest.



Vicente RL, Gullón S, Marin S, Mellado RP. The three Streptomyces lividans HtrA-like proteases involved in the secretion stress response act in a cooperative manner. PLoS One 2016; 11: e0168112

Valverde JR, Gullón S, Mellado RP. Looking for rhizobacterial ecological indicators in agricultural soils using 16S rRNA metagenomic amplicon data. PLoS One 2016; 11: e0165204

Gullón S, Vicente RL, Valverde JR, Marín S, Mellado RP. Exploring the feasibility of the Sec route to secrete proteins using the Tat route in Streptomyces lividans. Mol Biotechnol 2015; 57: 931-938

Gullón S, Marín S, Mellado RP. Overproduction of a model Sec-and Tat-Dependent secretory protein elicits different cellular responses in Streptomyces lividans. PLoS One 2015; 10: e0133645

Valverde JR, Marin S, Mellado RP. Effect of herbicide combinations on Bt-maize rhizobacterial diversity. J Microbiol Biotechnol 2014; 24:1473-1483


215 Figure 1The group continued to focus its research on the physiological and molecular characterisation of the main protein secretion mechanism (Sec system) of the soil Gram-positive bacteria Streptomyces lividans, widely used in industry as an efficient producer of extracellular hydrolytic enzymes and other compounds of industrial interest. Secretory protein overproduction triggers a secretion stress response, eliciting the synthesis of three specific proteases that degrade misfolded proteins, and a stringent response in Streptomyces.

Bacterial lipoproteins are a specialized class of membrane proteins reported to play a pivotal role in bacterial cell physiology, including protein folding. Absence of functional type II signal peptidase (Lsp), which cleaves the lipoprotein signal peptide, apparently produces a translocase blockage, as determined by the amount of the overproduced alpha-amylase that clearly accumulates on the internal surface of the membrane. As a result of the translocase blockage, Lsp deficiency reduces synthesis of secretory proteins in S. lividans, as is the case when the cell is deficient in the translocase complex (SecG mutant strain) or the major type I signal peptidase (SipY mutant strain). The lsp mutation also triggers a stringent response, as the absence of functional SBP lipoproteins causes non-sensing of solutes (nutrients) in the culture medium. These findings are of particular relevance with respect to characterising potential bottlenecks in S. lividans secretion and optimising S. lividans for the overproduction of secretory proteins of industrial application.

For a number of years, we have monitored the rhizobacterial communities of transgenic maize tolerant to glyphosate. In a new research line, we identified the most attractive method-combination workflow to analyse next generation sequencing results from rhizobacterial community experimental data, depending on sequence variability number and length. The worldwide increase in glyphosate-resistant weed populations led to new cultivation strategies based on combinations of pre- and post-emergence herbicides. Over a one-year cultivation cycle, we evaluated the impact of several herbicide combinations on the rhizobacterial community of glyphosate-tolerant Bt-maize and compared them to those of untreated or glyphosate-treated soils, and analysed the resilience of the microbial communities by comparing their relative composition at the end of the cultivation cycle.


 Lab 215 fotoRed 

Rafael P. Mellado Principal investigator
Sonia Gullón Postdoctoral scientist
Silvia Marín Technicians

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