Overview

The nine partners from academia and industry, that originate from six European countries, support and

drive the novel scientific movement of ‘biointelligence’ which reflects the conversion of biotechnology,

information technology including AI and automation technology. It is this biointelligence mindset that

makes up the core of BIOS and that accelerates strain and bioprocess engineering for producing novel

fine chemicals and commodities in a sustainable manner. BIOS makes intensive use of hybrid learning

to fully exploit the experimental data which are generated in an automated fashion. The project brings

together experts from molecular and synthetic biology, systems metabolic engineering, microbiology,

biochemical and bioprocess engineering, chemistry, and life cycle assessment.

The dedicated team has one collective goal: to replace current fossil routes by sustainable microbial

processes with the help of the biointelligent mindset. Soon, progress of BIOS will be made publicly

available through different channels.

WP 1 - Project Management

Lead:

University of Stuttgart & LifeGlimmer GmbH

Objectives:

a) to provide a sound and flexible structure for operational management and technical vitality of the project, encompassing management tasks on contractual, financial, legal, technical, administrative and ethical levels.

b) to provide and foresee a data management plan for the project according to FAIR principles

c) to initiate and supervise the subcontracting for the semantic BIOS communication platform

c) to provide an effective risk management strategy to avoid deviations from the work plan.

d) to respond to opportunities through an active innovation management

WP 2 - Digital Twinning

Lead:

University of Stuttgart

Objectives:

The creation of a Digital Twin of cellular and bioprocesses resulting robust and scalable biomanufacturing. Hybrid digital twins merging AI and mechanistic models will be created by:

a) acquisition of (existing/new) sensor, performance, and stress data

b) constraining protein formation with maximum metabolic capacities

c) detailed kinetic and process modelling

d) testing different AI approaches to complement mechanistic modelling

e) merging AI and mechanistic models

f) deploy gene manipulation sets for strain engineering

g) implementing self-sufficient control systems in autonomous bio-manufacturing approaches for the regulation of nutrient supply and environmental conditions

h) developing an approach for actionable knowledge to narrow the feasible variable and parameter space so as to identify when change in either strain or environmental conditions must occur.

WP 3 - Bioware Engineering

Lead:

Wageningen University

Objectives:

To develop and apply the tools for bioware engineering by

a) developing dedicated genetic and genome engineering tools for P. putida

b) automating those tools in robotics (laying the basis for extension to other Gram-negative bacteria)

c) developing a small-scale electroporation device for robotic application

d) applying those tools for targeted strain engineering

e) standardize procedures & installing check points

WP 4 - Biosensors & -metrics

Lead:

VTT Technical Research Centre of Finland

Objectives:

To access and use quantitative metrics of biosensing by

a) engineering promoter strength and measuring quantitative read-outs

b) at line measuring in vivo transcripts

c) installing standardization protocols to ensure data exchangeability

WP 5 - Adaptive Laboratory Evolution (ALE) & Stress Tests

Lead:

University of Tartu

Objectives:

To ensure robust strain design by

a) analysing engineered P. putida stress response to substrates, intermediates and products of the test cases

b) increasing roubustness and toughening strain performance by smart ALE selection

c) recycling cellular long-term response to bioware engineering

d) establish an AI-derived automated platform for optimization of ALE experimental design and execution

WP 6 - Hybrid Learning

Lead:

MICALIS Institute

Objectives:

To learn from experimental feedback by

a) finetuning structures & parameters of mechanistic models

b) training AI approaches

c) defining best interaction modes between mechanistic models and AI

WP 7 - Valorisation

Lead:

Ingenza Ltd

Objectives:

To exploit cellular production capacities in decentralized self-controlled bioprocesses by

a) engineering production strains for the production of terpenoids, tailored polymers, and methacrylates

b) developing a bioprocess with promising production strains

c) using hybrid digital twins for self-controlled autonomous production

WP 8 - Life Cycle Engineering

Lead:

Fraunhofer Institute

Objectives:

To balance and quantify the ecological impact of the innovative approach by carrying out life cycle analysis (LCA) of the novel bioproduction approaches by comparison of the novel bio-manufacturing approach with a conventional manufacturing method of the selected product or a comparable product in terms of sustainability.

WP 8 - Life Cycle Engineering

Lead:

Fraunhofer Institute

Objectives:

To balance and quantify the ecological impact of the innovative approach by carrying out life cycle analysis (LCA) of the novel bioproduction approaches by comparison of the novel bio-manufacturing approach with a conventional manufacturing method of the selected product or a comparable product in terms of sustainability.

WP 10 - Ethics

University of Stuttgart