Saccharomyces cerevisiae : Evoutions in Bio Sciences

Saccharomyces cerevisiae :

Evoutions in Bio Sciences

• Ecology

• Quantitative ecology

• Physiology,

• Quantitative biology

• Systemic Biology

• Holistic Biology

MICROBIAL/BIO REACTOR ENGINEERING:A BASIC TOOL FOR KNOWLEDGE IN HOLISTIC BIOLOGY

• G.Goma,S Guillouet,C Jouve,J L Uribellarea

• Laboratoire d ingenierie des systémes biologique et des procédés

• UMR CNRS,INRA,INSA

Microbial Engineering:a part of biotechnologies

• Find and improve the microorganisms for bio processing

• Find the conditions of bio processing where the microrganism is economicaly performant

• A multidisciplinary approach

• A contraint : find the bottlenecks,eliminate them

• An obligation:need of handling a complete tool box:from genes to bioproducts and bioprocess

What kind of technological strategy?

• Low tech ?

• High tech ?

• Right tech for the goal

The IB Value Chain

The steps

• Factory and his environment

• The reactors ,biorector:biocatalist,srategy

• Raw materials and biocatalist,bioreaction engineering

• The biocatalist

• Global implementation ;find the differents bottleneks and solve the problems

• Need a tool box,and combining experimentals datas(strategy?) and simulations

Industrial (White) Biotechnology

Dual use of fermentors

• RPM
• Qair
• Pressure
• CO2, O2 ?
• Gas balance
• OD?
• Ph (controlled)
• Temperature

• For this 2 controlled parameters, the analysis of the « work » of the control regulator gives informations

Metabolic descriptor

• Mass conservation

• Elemental biologicals reactions

• Macroscopic kinetics

• Matrix of reactions combining kinetics and stoechiometry of elemental reaction of metabolic pathways

• Combining kinetics observed by on line measurements by robusts sensors evaluation of metabolics fluxes « on line » and nutritionals needs

• Identification of some bottlenecks

Predictive modelisation and implementation of microbial processes

Prerequisite to “Systemic Biology”

Top Down strategy

• Fit the macroscopic environnment,bioreactor

• Find reproducible conditions:signature recognition

• Biokinetics

• Quantitative physiologie

• Metabolic pathways

• Proteomic

• transcriptomics

Motivation

Identification and Classification of Physiological States

• A bottlenek for « the omics »studies,for control strategies and « quality »

• Morphometry

• Kinetics and stoechiometrics « parameters »

• Differentiation of biologicals and environmental effects

Yeast :Axenic culture gives a population production linked to some mechanims

The Tool box

• Bio: the “omics”

• +

• Traditional technologies

• +

• mathematical tools

• “the rule of innovation”

Microbial engineering is multidisciplinary : need of quantitative and “system” biology

Dual use of fermentors

Cell production kinetic

Cell and glucose ethanol concentration vs time (Fed batch with nutritional strategy)

Study of a reference fermentation

How does works are integrated ?

Studying the fast biological responses ...

The hyper yeast

Automate utilisé pour la supervision

Perspective : Use of behavioural modelling

Perspective : Use of behavioural modelling

Introduction

• What is life

• Diference beetwen an abiotic and biotic system

• Ecosystem

• Unicity and diversity of lives objects

• Life by a whole,studies mainly on the parts

• Remenber Z Zidane

• Reductionism,integrativ biology,systemic biology, holistic biology

Bacteria

• Bacteria
• Yeast
• Fungi
• Eucaryotic cells
• In every case
• The basic law of biokinetics and stoechiometry are the same
• But, every case have rules of utilisation with typical profile

Predictive modelisation and implementation of microbial processes

Study of a fermentation of reference

Study of a fermentation of reference

Heterogeneities:gradients(flux,stocks,,,) :microbe population

Top Down strategy

• Fit the macroscopic environnment,bioreactor

• Find reproducible conditions:signature recognition

• Biokinetics

• Quantitative physiologie

• Metabolic pathways

• Proteomic

• transcriptomics

Synthesis

• Engineers Top down strategies

• Biologists,bottum up , bioinformatics!!!!!!!!!

• Both strategies are necessary

Basic concepts

Tackling complexity in industrial microbiology for bioprocessing