Reshaping microbial biotechnology

A multidisciplinary and multilevel approach

The aim of our research lines

Discover our four study fields

The aim of our research lines

Discover our four study fields

Increasing the completeness and scope of metabolic reconstructions

Building metabolic models with wider capabilities

We are committed to building a niche-specific collection of standardised and highly reproducible metabolic models. In pursuit of this goal, we have dedicated ourselves to developing high-quality models for a wide range of metabolically diverse microorganisms. We place particular emphasis on expanding the scope of metabolic modelling by incorporating new modules that capture important aspects of microbial metabolism. 

This includes modeling the generation of endogenous reactive oxygen species, underground metabolism, metabolic heterogeneity, and condition-specific biomass production. By incorporating these additional components, we aim to enhance the accuracy and applicability of our models, enabling a deeper understanding of microbial physiology and facilitating the design of innovative biotechnological and clinical solutions.

Increasing the completeness and scope of metabolic reconstructions

Building metabolic models with wider capabilities

We are committed to building a niche-specific collection of standardised and highly reproducible metabolic models. In pursuit of this goal, we have dedicated ourselves to developing high-quality models for a wide range of metabolically diverse microorganisms. We place particular emphasis on expanding the scope of metabolic modelling by incorporating new modules that capture important aspects of microbial metabolism. 

This includes modeling the generation of endogenous reactive oxygen species, underground metabolism, metabolic heterogeneity, and condition-specific biomass production. By incorporating these additional components, we aim to enhance the accuracy and applicability of our models, enabling a deeper understanding of microbial physiology and facilitating the design of innovative biotechnological and clinical solutions.

Disentangling the driving forces behind metabolic processes

Understanding and exploiting the multioptimality of microbial metabolism

Microbial metabolism operates and evolves under the trade-off between two principles: optimality under one given condition and minimal adjustment between conditions. These principles give rise to a three-dimensional space characterised by competing objectives: growth, robustness, and adaptability. At our lab, we are dedicated to deciphering the intricate relationship between metabolic robustness, adaptability, and optimality in microbial metabolism.

We seek to investigate the mechanisms underlying metabolic cycles that promote high robustness in bacteria and explore how metabolic heterogeneity contributes to microbial survival in the face of perturbations. By gaining a deeper understanding of these fundamental aspects, we aim to apply this knowledge to diverse fields such as biotechnology and clinical microbiology. Our ultimate goal is to leverage this newfound understanding to develop innovative solutions for a wide range of applications.

Disentangling the driving forces behind metabolic processes

Understanding and exploiting the multioptimality of microbial metabolism

Microbial metabolism operates and evolves under the trade-off between two principles: optimality under one given condition and minimal adjustment between conditions. These principles give rise to a three-dimensional space characterised by competing objectives: growth, robustness, and adaptability. At our lab, we are dedicated to deciphering the intricate relationship between metabolic robustness, adaptability, and optimality in microbial metabolism.

We seek to investigate the mechanisms underlying metabolic cycles that promote high robustness in bacteria and explore how metabolic heterogeneity contributes to microbial survival in the face of perturbations. By gaining a deeper understanding of these fundamental aspects, we aim to apply this knowledge to diverse fields such as biotechnology and clinical microbiology. Our ultimate goal is to leverage this newfound understanding to develop innovative solutions for a wide range of applications.

Studying microbiome-wide relationships

System level analysis and designing microbial communities

The division of labor allows an expanded complexity and functionality in microorganisms. Guided by these interesting features, our research focuses on two key objectives. Firstly, we aim to unravel the mechanisms underlying the emergence of complex capabilities within microbial populations and communities. By studying how microorganisms interact and coordinate their activities, we seek to understand the factors that contribute to their expanded functionality. Secondly, we strive to harness and engineer this supracellular-level functionality for various biotechnological and clinical applications.

To achieve this, we have developed a comprehensive suite of systems biology tools and evolutionary engineering frameworks. Our research finds practical application in multiple areas. For instance, we are working towards the valorization of complex polymers like lignin and plastic wastes, aiming to develop sustainable strategies for their use. Additionally, we focus on cost-effective production of plant-based secondary metabolites and the development of animal-free, sustainable ingredients for the food, beverage and nutraceutical industries.

Studying microbiome-wide relationships

System level analysis and designing microbial communities

The division of labor allows an expanded complexity and functionality in microorganisms. Guided by these interesting features, our research focuses on two key objectives. Firstly, we aim to unravel the mechanisms underlying the emergence of complex capabilities within microbial populations and communities. By studying how microorganisms interact and coordinate their activities, we seek to understand the factors that contribute to their expanded functionality. Secondly, we strive to harness and engineer this supracellular-level functionality for various biotechnological and clinical applications.

To achieve this, we have developed a comprehensive suite of systems biology tools and evolutionary engineering frameworks. Our research finds practical application in multiple areas. For instance, we are working towards the valorization of complex polymers like lignin and plastic wastes, aiming to develop sustainable strategies for their use. Additionally, we focus on cost-effective production of plant-based secondary metabolites and the development of animal-free, sustainable ingredients for the food, beverage and nutraceutical industries.

Broadening applications using AI and automation

Developing a DNA biofoundry towards the AI-guided exploration of microbial chemical space.

We are actively involved in the development of a DNA biofoundry (CNBio) that integrates advanced automation, synthetic biology, evolutionary engineering and artificial intelligence (AI) to explore the untapped potential of microbial metabolism. Our goal is to go beyond the limited set of known biochemical transformations and uncover new metabolic pathways that can expand the metabolic space suitable for biotechnological and medical applications. Through the use of advanced automation and synthetic biology techniques, we can design and build genetic circuits and pathways in a systematic and precise manner. This allows us to engineer microorganisms with enhanced metabolic capabilities, opening up new possibilities for the production of valuable compounds. Furthermore, the AI-guided approach enables us to explore the vast chemical landscape of potential transformations and accelerate the discovery and optimization of novel microbial metabolic capabilities.

Broadening applications using AI and automation

Developing a DNA biofoundry towards the AI-guided exploration of microbial chemical space.

We are actively involved in the development of a DNA biofoundry (CNBio) that integrates advanced automation, synthetic biology, evolutionary engineering and artificial intelligence (AI) to explore the untapped potential of microbial metabolism. Our goal is to go beyond the limited set of known biochemical transformations and uncover new metabolic pathways that can expand the metabolic space suitable for biotechnological and medical applications. Through the use of advanced automation and synthetic biology techniques, we can design and build genetic circuits and pathways in a systematic and precise manner. This allows us to engineer microorganisms with enhanced metabolic capabilities, opening up new possibilities for the production of valuable compounds. Furthermore, the AI-guided approach enables us to explore the vast chemical landscape of potential transformations and accelerate the discovery and optimization of novel microbial metabolic capabilities.

The initiatives that move us forward

Explore our project’s catalogue

The initiatives that move us forward

Explore our project’s catalogue

Ongoing projects

PROMISEANG
Horizon Europe

Alternative PROteins from MIcrobial fermentation of non-conventional SEA sources for Next-Generation food, feed and non-food bio-based applications (PROMISEANG)

  • Project Ref. 101112378
  • HORIZON-JU-CBE-2022
  • PI Juan Nogales (CNB-CSIC)
  • 01/09/2023-31/08/27
PROMISEANG is a 48-month project that aims to develop novel alternative proteins from marine underexploited sources (marine invertebrate and macroalgae discards and industrial biowastes) through biomass fermentation, generating new protein-enriched microbial biomass (known as single cell proteins, SCP), meeting market requirements for food, feed, and non-food (biomedicine, pharma and cosmetic) bio-based applications. Specifically, SBG is in charge of engineering optimal microbial biocatalyst based on evolved microbiomes.
deCYPher
Horizon Europe

Decipher cytochrome P450 enzymes (CYPs) by digital tools to produce flavonoids and terpenoids (DeCYPher)

  • Project Ref. 101081782
  • HORIZON-CL6-2022-CIRCBIO-02-two-stageI
  • PI Juan Nogales (CNB-CSIC)
  • 01/09/2023-31/08/27

The deCYPher project is developing a standardised platform to profoundly implement artificial intelligence (AI) and machine learning (ML) techniques to overcome current hurdles in industrial biotechnology and truly unlock the full potential in biotech engineering. SBG is involved in the application of this platform to solve a pertinent problem in the microbial production of plant secondary metabolites, namely the bio-based production of flavonoids. The goal is to understand and functionally apply the oxygenation of the plant metabolite scaffolds mediated by cytochrome P450 enzymes (CYPs) in the context of synthetic microbial compartments.

PROMICON
H2020

Harnessing the power of nature through productive microbial consortia in biotechnology: Measure, Model, Master (PROMICON)

  • Project Ref. 101000733
  • EU H2020-FNR-2020-2
  • Co-PI CSIC Juan Nogales
  • 01/06/2021-31/05/2025

The aim of the PROMICON project is to learn from nature how microbiomes function through latest and novel methods in order to steer their growth towards production of biopolymers, energy carriers, drop-in feedstocks and antimicrobial molecules. PROMICON will use the existing microbiomes and then use them in top-down and bottom-up approaches for industrial application.SBG group is developing new computational tools to extract information from metagenomics data and construct highly curated metabolic models from environmental microbiomes. Additional SBG is engineering synthetic autotrophic microbial consortia to produce a new generation of functionalized bioplastics.

Synthetic microbial consortia-based platform for flavonoids production using synthetic biology (SynBio4Flav)

  • Project Ref. 814650
  • EU H2020-NMBP/0500
  • Coordinator and CSIC PI Juan Nogales (CNB-CSIC)
  • 01/03/2019-28/02/2023

By using synthetic biology, the SynBio4Flav project aims to provide a cost-effective alternative to current flavonoid production. SynBio4Flav’s scientific challenge is to produce flavonoids by breaking down their complex biosynthetic pathways into standardized specific parts, which can be transferred to engineered microorganisms within Synthetic Microbial Consortia to promote flavonoid assembly through distributed catalysis. The project’s ultimate goal is to deliver a paradigm shift in biotechnological manufacturing of complex natural chemicals. SBG is the lead coordinator and is in charge of the BIO computer-aided design of synthetic microbial consortia overproducing functionalized flavonoids.

Rob3D
National projects

Exploiting the tridimensional optimality of microbial metabolism towards the sustainable production of natural products (Rob3D)

  • Project Ref. PID2022-139247OB-I00
  • MCI. PI Juan Nogales (CNB-CSIC)
  • 01/9/2023-31/08/2026

Rob3D aims to leverage emergent system properties, such as robustness and adaptability, within the realm of synthetic biology, to facilitate distributed catalysis through the utilization of adjustable monoclonal heterogeneous microbial populations for flavonoid production. To achieve this, SBG is initially deconstruct the inherent radial biosynthetic pathway of flavonoids into a linear configuration, thereby streamlining its complexity. Subsequently, we will introduce a dynamic regulation reliant on O2 and ROS, orchestrating the synthesis of targeted flavonoids within synthetically engineered P. putida populations. This regulation will be achieved through the implementation of Toggle-switch circuits, enhancing the precision and control of the process.

SyCoSyS
National projects

Optimizing the Synechococcus-driven microbial Consortia with biotechnological applications by using Systems and Synthetic Biology tools (SyCoSys)

  • Project Ref. TED2021-130689B-C33
  • MCI. PI Juan Nogales (CNB-CSIC)
  • 01/12/2022-30/11/2024

SyCoSys aims to dissect, streamline, and model the intricate energy and matter flows within engineered synthetic consortia, all while optimizing operational conditions within innovative microbial community-based bioreactors. By synergizing systems and synthetic biology methodologies, SyCoSys strives to yield mechanistic insights into the engineering of synthetic microbiomes. A pioneering feature of SyCoSys involves the development of a net-zero CO2 emissions bioprocess, leveraging engineered cyanobacteria to facilitate the conversion of CO2 into readily metabolizable sugars. In a continuous operation, the organic carbon produced by cyanobacteria will serve as nourishment for P. putida, acting as a specialized cell factory optimized for the overproduction of cyclic terpenoid precursors, essential components of terephthalic acid—an integral constituent of the widely utilized plastic, Polyethylene terephthalate (PET). Consequently, SyCoSys marks a significant stride towards the realization of Biobased-PET production.

MIXUP
H2020

MIXed plastics biodegradation and UPcycling using microbial communities (MIXUP)

  • Project Ref. 870294
  • EU H2020-NMBP-BIO-CN-2019
  • Co-PI CSIC Juan Nogales (CNB-CSIC)
  • 01/2020-12/2024

The main idea of MIX-UP (MIXed plastics biodegradation and UPcycling using microbial communities) is to showcase a novel approach for plastic recycling and therefore addresses one of the greatest challenges of our time: the establishment of a circular (bio)-economy for plastics. The continuing demand for plastic products, the lack of appropriate recycling and the ubiquitous pollution of the environment with plastic waste pose a global challenge. In this context, SGB is developing new synthetic biology tools and computational pipelines for the engineering of metabolically heterogeneous P. putida populations and synthetic microbial consortia for the efficient upcycling of PET

Finished projects

LIAR
Horizon Europe

Design and build a proof-of-concept ‘living architecture’ whose targeted breakthrough is to transform our habitats from inert spaces into programmable sites

  • 686585, Living Architecture (LIAR). EU FETOPEN-RIA-2014-2015
  • FET-Open research projects. CSIC PI Juan Nogales (CIB-CSIC and CNB-CSIC).
  • 01/04/2016-31/06/2019

The goal of project LIAR was to design and build a proof-of-concept ‘living architecture’ whose targeted breakthrough is to transform our habitats from inert spaces into programmable sites. LIAR was developed as a modular bioreactor-wall, based on the operational principles of microbial fuel cell technology and synthetic ‘consortia’ of microbes. LIAR was designed as an early stage technology, aimed at providing a foundational platform for the exploitation of synthetic biology principles to engineer synthetic microbial communities. In this context, the SBG introduced an innovative computational framework, marking the pioneering creation of a design and implementation strategy for synthetic microbial consortia using metabolic modelling. Furthermore, the group successfully realized a photoautotrophic synthetic microbial consortium specifically designed to purify household grey water, showcasing the practical applications of this approach.

MENTHOL 
H2020

Metabolic heterogeneity of monoclonal bacterial cells as a biotechnological tool to produce natural compounds (MENTHOL)

  • Project Ref. 101027389
  • EU H2020-MSCA-IF
  • Coordinator and Co-PI CSIC Juan Nogales
  • 01/06/2021-31/05/2023

MENTHOL aimed to change current paradigms of biotechnological production of complex plant natural compounds, specifically isoprenoids such as limonene, menthol, and p-cymene. MENTHOL main innovation lies in the synthetic decoupling of the complex biosynthetic pathways of these compounds into a distributed catalysis within monoclonal heterogeneous bacterial populations. To achieve such ambitious goal, in this project we applied cutting-edge systems and synthetic biology tools to engineer programmable metabolic heterogeneity inside a monoclonal population of Pseudomonas putida, thus promoting the division of labour during the production of limonene, menthol, and p-cymene using waste cooking oils as economic and reliable renewable feedstock.

IBISBA
H2020

Industrial Biotechnology Innovation and Synthetic Biology Accelerator (IBISBA1.0)

  • Project Ref. 730976
  • EU INFRAIA-02-2017
  • Co-PI CSIC Juan Nogales (CNB-CSIC)
  • 12/2017-11/2021

IBISBA was a European initiative with the goal of establishing a pan-European research infrastructure focused on advancing Industrial Biotechnology. Following its successful implementation, this platform now offers a unified entryway for researchers from both academic and industrial sectors worldwide, granting them access to comprehensive services encompassing the entire spectrum of bioprocess development. Notably, within this framework, SBG offers specialized services in metabolic modelling as well as the design and implementation of microbial catalysis through Bio-CAD approaches.

RobExplode 
National projects

System analysis and biotechnological applications of bacterial metabolic robustness at supracellular level (RobExplode)

  • Project Ref. PID2019-108458RB-I00
  • MCIU. PI Juan Nogales (CNB-CSIC)
  • 01/06/2020-31/5/2023

RobExplode aimed to go further in the study of the metabolic robustness in P. putida and understand how metabolic heterogeneity emerges, at population level. The new knowledge acquired was used for designing a pipeline driving to control and taming of metabolic heterogeneity in bacteria and finally to develop a standard procedure for engineering heterogeneous P. putida populations a la carte for biotechnological proposes. RobExplode targets were the production of raspberry ketone and glucogallin, two complex and add-value plant natural products. 

RobDcode 
National projects

System level analysis of the metabolic robustness in bacteria (RobDcode)

  • Project Ref. BIO2014-59528-JIN
  • MINECO
  • PI Juan Nogales (CIB-CSIC and CNB-CSIC)
  • 16/10/2015-14/10/2018

The understanding of the genotype-phenotype relationship is a fundamental biological question, widely studied, but still not understood in all its dimension. The existence of emergent systems properties largely hampers the linearity of this relationship making it mandatory the study of such properties to fully understand the biological systems. The robustness, understood as the property that allows the systems to maintain their functions despite external and internal perturbations, is a system-level phenomenon ubiquitously observed in living systems, however it is still poorly understood at molecular level. RobDcode was the foundational project of SBG and undertook the exploration of molecular mechanisms that confer robustness upon bacterial systems. This endeavour embraced an integrative approach spanning microbiological, molecular, and systems biology strategies. The outcomes of this project yielded significant insights, including the identification of robustness cycles. Contrary to being mere futile loops, these cycles were established to play a pivotal role in furnishing metabolic resilience to Pseudomonas putida amid various environmental disturbances.

Ongoing projects
PROMISEANG
Horizon Europe

Alternative PROteins from MIcrobial fermentation of non-conventional SEA sources for Next-Generation food, feed and non-food bio-based applications (PROMISEANG)

  • Project Ref. 101112378
  • HORIZON-JU-CBE-2022
  • PI Juan Nogales (CNB-CSIC)
  • 01/09/2023-31/08/27
PROMISEANG is a 48-month project that aims to develop novel alternative proteins from marine underexploited sources (marine invertebrate and macroalgae discards and industrial biowastes) through biomass fermentation, generating new protein-enriched microbial biomass (known as single cell proteins, SCP), meeting market requirements for food, feed, and non-food (biomedicine, pharma and cosmetic) bio-based applications. Specifically, SBG is in charge of engineering optimal microbial biocatalyst based on evolved microbiomes.
deCYPher
Horizon Europe

Decipher cytochrome P450 enzymes (CYPs) by digital tools to produce flavonoids and terpenoids (DeCYPher)

  • Project Ref. 101081782
  • HORIZON-CL6-2022-CIRCBIO-02-two-stageI
  • PI Juan Nogales (CNB-CSIC)
  • 01/09/2023-31/08/27

The deCYPher project is developing a standardised platform to profoundly implement artificial intelligence (AI) and machine learning (ML) techniques to overcome current hurdles in industrial biotechnology and truly unlock the full potential in biotech engineering. SBG is involved in the application of this platform to solve a pertinent problem in the microbial production of plant secondary metabolites, namely the bio-based production of flavonoids. The goal is to understand and functionally apply the oxygenation of the plant metabolite scaffolds mediated by cytochrome P450 enzymes (CYPs) in the context of synthetic microbial compartments.

PROMICON
H2020

Harnessing the power of nature through productive microbial consortia in biotechnology: Measure, Model, Master (PROMICON)

  • Project Ref. 101000733
  • EU H2020-FNR-2020-2
  • Co-PI CSIC Juan Nogales
  • 01/06/2021-31/05/2025

The aim of the PROMICON project is to learn from nature how microbiomes function through latest and novel methods in order to steer their growth towards production of biopolymers, energy carriers, drop-in feedstocks and antimicrobial molecules. PROMICON will use the existing microbiomes and then use them in top-down and bottom-up approaches for industrial application.SBG group is developing new computational tools to extract information from metagenomics data and construct highly curated metabolic models from environmental microbiomes. Additional SBG is engineering synthetic autotrophic microbial consortia to produce a new generation of functionalized bioplastics.

Synthetic microbial consortia-based platform for flavonoids production using synthetic biology (SynBio4Flav)

  • Project Ref. 814650
  • EU H2020-NMBP/0500
  • Coordinator and CSIC PI Juan Nogales (CNB-CSIC)
  • 01/03/2019-28/02/2023

By using synthetic biology, the SynBio4Flav project aims to provide a cost-effective alternative to current flavonoid production. SynBio4Flav’s scientific challenge is to produce flavonoids by breaking down their complex biosynthetic pathways into standardized specific parts, which can be transferred to engineered microorganisms within Synthetic Microbial Consortia to promote flavonoid assembly through distributed catalysis. The project’s ultimate goal is to deliver a paradigm shift in biotechnological manufacturing of complex natural chemicals. SBG is the lead coordinator and is in charge of the BIO computer-aided design of synthetic microbial consortia overproducing functionalized flavonoids.

Rob3D
National projects

Exploiting the tridimensional optimality of microbial metabolism towards the sustainable production of natural products (Rob3D)

  • Project Ref. PID2022-139247OB-I00
  • MCI. PI Juan Nogales (CNB-CSIC)
  • 01/9/2023-31/08/2026

Rob3D aims to leverage emergent system properties, such as robustness and adaptability, within the realm of synthetic biology, to facilitate distributed catalysis through the utilization of adjustable monoclonal heterogeneous microbial populations for flavonoid production. To achieve this, SBG is initially deconstruct the inherent radial biosynthetic pathway of flavonoids into a linear configuration, thereby streamlining its complexity. Subsequently, we will introduce a dynamic regulation reliant on O2 and ROS, orchestrating the synthesis of targeted flavonoids within synthetically engineered P. putida populations. This regulation will be achieved through the implementation of Toggle-switch circuits, enhancing the precision and control of the process.

SyCoSyS
National projects

Optimizing the Synechococcus-driven microbial Consortia with biotechnological applications by using Systems and Synthetic Biology tools (SyCoSys)

  • Project Ref. TED2021-130689B-C33
  • MCI. PI Juan Nogales (CNB-CSIC)
  • 01/12/2022-30/11/2024

SyCoSys aims to dissect, streamline, and model the intricate energy and matter flows within engineered synthetic consortia, all while optimizing operational conditions within innovative microbial community-based bioreactors. By synergizing systems and synthetic biology methodologies, SyCoSys strives to yield mechanistic insights into the engineering of synthetic microbiomes. A pioneering feature of SyCoSys involves the development of a net-zero CO2 emissions bioprocess, leveraging engineered cyanobacteria to facilitate the conversion of CO2 into readily metabolizable sugars. In a continuous operation, the organic carbon produced by cyanobacteria will serve as nourishment for P. putida, acting as a specialized cell factory optimized for the overproduction of cyclic terpenoid precursors, essential components of terephthalic acid—an integral constituent of the widely utilized plastic, Polyethylene terephthalate (PET). Consequently, SyCoSys marks a significant stride towards the realization of Biobased-PET production.

MIXUP
H2020

MIXed plastics biodegradation and UPcycling using microbial communities (MIXUP)

  • Project Ref. 870294
  • EU H2020-NMBP-BIO-CN-2019
  • Co-PI CSIC Juan Nogales (CNB-CSIC)
  • 01/2020-12/2024

The main idea of MIX-UP (MIXed plastics biodegradation and UPcycling using microbial communities) is to showcase a novel approach for plastic recycling and therefore addresses one of the greatest challenges of our time: the establishment of a circular (bio)-economy for plastics. The continuing demand for plastic products, the lack of appropriate recycling and the ubiquitous pollution of the environment with plastic waste pose a global challenge. In this context, SGB is developing new synthetic biology tools and computational pipelines for the engineering of metabolically heterogeneous P. putida populations and synthetic microbial consortia for the efficient upcycling of PET

Finished projects
LIAR
Horizon Europe

Design and build a proof-of-concept ‘living architecture’ whose targeted breakthrough is to transform our habitats from inert spaces into programmable sites

  • 686585, Living Architecture (LIAR). EU FETOPEN-RIA-2014-2015
  • FET-Open research projects. CSIC PI Juan Nogales (CIB-CSIC and CNB-CSIC).
  • 01/04/2016-31/06/2019

The goal of project LIAR was to design and build a proof-of-concept ‘living architecture’ whose targeted breakthrough is to transform our habitats from inert spaces into programmable sites. LIAR was developed as a modular bioreactor-wall, based on the operational principles of microbial fuel cell technology and synthetic ‘consortia’ of microbes. LIAR was designed as an early stage technology, aimed at providing a foundational platform for the exploitation of synthetic biology principles to engineer synthetic microbial communities. In this context, the SBG introduced an innovative computational framework, marking the pioneering creation of a design and implementation strategy for synthetic microbial consortia using metabolic modelling. Furthermore, the group successfully realized a photoautotrophic synthetic microbial consortium specifically designed to purify household grey water, showcasing the practical applications of this approach.

MENTHOL 
H2020

Metabolic heterogeneity of monoclonal bacterial cells as a biotechnological tool to produce natural compounds (MENTHOL)

  • Project Ref. 101027389
  • EU H2020-MSCA-IF
  • Coordinator and Co-PI CSIC Juan Nogales
  • 01/06/2021-31/05/2023

MENTHOL aimed to change current paradigms of biotechnological production of complex plant natural compounds, specifically isoprenoids such as limonene, menthol, and p-cymene. MENTHOL main innovation lies in the synthetic decoupling of the complex biosynthetic pathways of these compounds into a distributed catalysis within monoclonal heterogeneous bacterial populations. To achieve such ambitious goal, in this project we applied cutting-edge systems and synthetic biology tools to engineer programmable metabolic heterogeneity inside a monoclonal population of Pseudomonas putida, thus promoting the division of labour during the production of limonene, menthol, and p-cymene using waste cooking oils as economic and reliable renewable feedstock.

IBISBA
H2020

Industrial Biotechnology Innovation and Synthetic Biology Accelerator (IBISBA1.0)

  • Project Ref. 730976
  • EU INFRAIA-02-2017
  • Co-PI CSIC Juan Nogales (CNB-CSIC)
  • 12/2017-11/2021

IBISBA was a European initiative with the goal of establishing a pan-European research infrastructure focused on advancing Industrial Biotechnology. Following its successful implementation, this platform now offers a unified entryway for researchers from both academic and industrial sectors worldwide, granting them access to comprehensive services encompassing the entire spectrum of bioprocess development. Notably, within this framework, SBG offers specialized services in metabolic modelling as well as the design and implementation of microbial catalysis through Bio-CAD approaches.

RobExplode 
National projects

System analysis and biotechnological applications of bacterial metabolic robustness at supracellular level (RobExplode)

  • Project Ref. PID2019-108458RB-I00
  • MCIU. PI Juan Nogales (CNB-CSIC)
  • 01/06/2020-31/5/2023

RobExplode aimed to go further in the study of the metabolic robustness in P. putida and understand how metabolic heterogeneity emerges, at population level. The new knowledge acquired was used for designing a pipeline driving to control and taming of metabolic heterogeneity in bacteria and finally to develop a standard procedure for engineering heterogeneous P. putida populations a la carte for biotechnological proposes. RobExplode targets were the production of raspberry ketone and glucogallin, two complex and add-value plant natural products. 

RobDcode 
National projects

System level analysis of the metabolic robustness in bacteria (RobDcode)

  • Project Ref. BIO2014-59528-JIN
  • MINECO
  • PI Juan Nogales (CIB-CSIC and CNB-CSIC)
  • 16/10/2015-14/10/2018

The understanding of the genotype-phenotype relationship is a fundamental biological question, widely studied, but still not understood in all its dimension. The existence of emergent systems properties largely hampers the linearity of this relationship making it mandatory the study of such properties to fully understand the biological systems. The robustness, understood as the property that allows the systems to maintain their functions despite external and internal perturbations, is a system-level phenomenon ubiquitously observed in living systems, however it is still poorly understood at molecular level. RobDcode was the foundational project of SBG and undertook the exploration of molecular mechanisms that confer robustness upon bacterial systems. This endeavour embraced an integrative approach spanning microbiological, molecular, and systems biology strategies. The outcomes of this project yielded significant insights, including the identification of robustness cycles. Contrary to being mere futile loops, these cycles were established to play a pivotal role in furnishing metabolic resilience to Pseudomonas putida amid various environmental disturbances.