Structured morphological modeling as a framework for rational strain design of Streptomyces speciesReport as inadecuate

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Antonie van Leeuwenhoek

, Volume 102, Issue 3, pp 409–423

First Online: 21 June 2012Received: 03 April 2012Accepted: 30 May 2012


Successful application of a computational model for rational design of industrial Streptomyces exploitation requires a better understanding of the relationship between morphology—dictated by microbial growth, branching, fragmentation and adhesion—and product formation. Here we review the state-of-the-art in modeling of growth and product formation by filamentous microorganisms and expand on existing models by combining a morphological and structural approach to realistically model and visualize a three-dimensional pellet. The objective is to provide a framework to study the effect of morphology and structure on natural product and enzyme formation and yield. Growth and development of the pellet occur via the processes of apical extension, branching and cross-wall formation. Oxygen is taken to be the limiting component, with the oxygen concentration at the tips regulating growth kinetics and the oxygen profile within the pellet affecting the probability of branching. Biological information regarding the processes of differentiation and branching in liquid cultures of the model organism Streptomyces coelicolor has been implemented. The model can be extended based on information gained in fermentation trials for different production strains, with the aim to provide a test drive for the fermentation process and to pre-assess the effect of different variables on productivity. This should aid in improving Streptomyces as a production platform in industrial biotechnology.

KeywordsMorphological modeling Fermentation Microscopy Enzyme Antibiotic SsgA List of symbolsVariablesAbranchBranch age h

AdiffDifferentiation age h

bintBranch formation interval m

cintCross-wall formation interval m

COOxygen concentration in fermentation broth kg-m

CXConcentration of biomass kg-m

CX,AConcentration of biomass, apical kg m

CX,BConcentration of biomass, subapical kg m

CX,HConcentration of biomass, hyphal kg m

dHyphal diameter m

dtTime step h

DO2,effEffective diffusion coefficient for oxygen m h

HGUHyphal growth unit

KOMicrobial saturation coefficient for oxygen kg m

LA,maxMaximum length of apical compartment m

OUROxygen uptake rate kg m h

PbranchProbability of branching % h

PbreakProbability of breaking % h

rRadius of pellet m

rtipDistance from pellet centre to tip m

rthresThreshold radius m

VHyphal segment volume m

YXOYield of biomass on oxygen kg kg

YXO,AYield of biomass on oxygen, apical kg kg

YXO,BYield of biomass on oxygen, subapical kg kg

YXO,HYield of biomass on oxygen, hyphal kg kg

Greek symbolsαi,maxMaximum linear apical extension rate of branch i m h

αi,maxAMaximum linear extension rate of branch i, apical compartment m h

αi,maxBMaximum linear extension rate of branch i, subapical compartment m h

αi,maxHMaximum linear extension rate of branch i, hyphal compartment m h

λshearShear force parameter

μMaximum specific hyphal growth rate h

ρxDensity of hyphae kg dw m

θPolar angle in spherical coordinates

φCone angle in spherical coordinates

Electronic supplementary materialThe online version of this article doi:10.1007-s10482-012-9760-9 contains supplementary material, which is available to authorized users.

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Author: Katherine Celler - Cristian Picioreanu - Mark C. M. van Loosdrecht - Gilles P. van Wezel


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