scholarly journals An evolutionary algorithm for designing microbial communities via environmental modification

2020 ◽  
Author(s):  
Alan R. Pacheco ◽  
Daniel Segrè

AbstractDespite a growing understanding of how environmental composition affects microbial community properties, it remains difficult to apply this knowledge to the rational design of synthetic multispecies consortia. This is because natural microbial communities can harbor thousands of different organisms and environmental substrates, making up a vast combinatorial space that precludes exhaustive experimental testing and computational prediction. Here, we present a method based on the combination of machine learning and dynamic flux balance analysis (dFBA) that selects optimal environmental compositions to produce target community phenotypes. In this framework, dFBA is used to model the growth of a community in candidate environments. A genetic algorithm is then used to evaluate the behavior of the community relative to a target phenotype, and subsequently adjust the environment to allow the organisms to more closely approach this target. We apply this iterative process to in silico communities of varying sizes, showing how it can rapidly identify environments that yield desired phenotypes. Moreover, this novel combination of approaches produces testable predictions for the in vivo assembly of microbial communities with specific properties, and can facilitate rational environmental design processes for complex microbiomes.

2021 ◽  
Vol 18 (179) ◽  
pp. 20210348
Author(s):  
Alan R. Pacheco ◽  
Daniel Segrè

Despite a growing understanding of how environmental composition affects microbial communities, it remains difficult to apply this knowledge to the rational design of synthetic multispecies consortia. This is because natural microbial communities can harbour thousands of different organisms and environmental substrates, making up a vast combinatorial space that precludes exhaustive experimental testing and computational prediction. Here, we present a method based on the combination of machine learning and metabolic modelling that selects optimal environmental compositions to produce target community phenotypes. In this framework, dynamic flux balance analysis is used to model the growth of a community in candidate environments. A genetic algorithm is then used to evaluate the behaviour of the community relative to a target phenotype, and subsequently adjust the environment to allow the organisms to approach this target. We apply this iterative process to thousands of in silico communities of varying sizes, showing how it can rapidly identify environments that yield desired taxonomic compositions and patterns of metabolic exchange. Moreover, this combination of approaches produces testable predictions for the assembly of experimental microbial communities with specific properties and can facilitate rational environmental design processes for complex microbiomes.


2020 ◽  
Vol 117 (10) ◽  
pp. 3006-3017 ◽  
Author(s):  
Carolina Shene ◽  
Paris Paredes ◽  
Liset Flores ◽  
Allison Leyton ◽  
Juan A. Asenjo ◽  
...  

2012 ◽  
Vol 110 (3) ◽  
pp. 792-802 ◽  
Author(s):  
K. Höffner ◽  
S. M. Harwood ◽  
P. I. Barton

2013 ◽  
Vol 163 (2) ◽  
pp. 637-647 ◽  
Author(s):  
E. Grafahrend-Belau ◽  
A. Junker ◽  
A. Eschenroder ◽  
J. Muller ◽  
F. Schreiber ◽  
...  

2018 ◽  
Author(s):  
Kevin Correia ◽  
Anna Khusnutdinova ◽  
Peter Yan Li ◽  
Jeong Chan Joo ◽  
Greg Brown ◽  
...  

ABSTRACTXylose is the second most abundant sugar in lignocellulose and can be used as a feedstock for next-generation biofuels by industry.Saccharomyces cerevisiae, one of the main workhorses in biotechnology, is unable to metabolize xylose natively but has been engineered to ferment xylose to ethanol with the xylose reductase (XR) and xylitol dehydrogenase (XDH) genes fromScheffersoymces stipitis. In the scientific literature, the yield and volumetric productivity of xylose fermentation to ethanol in engineeredS. cerevisiaestill lagsS. stipitis, despite expressing of the same XR-XDH genes. These contrasting phenotypes can be due to differences inS. cerevisiae’sredox metabolism that hinders xylose fermentation, differences inS. stipitis’redox metabolism that promotes xylose fermentation, or both. To help elucidate howS. stipitisferments xylose, we used flux balance analysis to test various redox balancing mechanisms, reviewed published omics datasets, and studied the phylogeny of key genes in xylose fermentation.In vivoandin silicoxylose fermentation cannot be reconciled without NADP phosphatase (NADPase) and NADH kinase. We identified eight candidate genes for NADPase.PHO3.2was the sole candidate showing evidence of expression during xylose fermentation. Pho3.2p and Pho3p, a recent paralog, were purified and characterized for their substrate preferences. Only Pho3.2p was found to have NADPase activity. Both NADPase and NAD(P)H-dependent XR emerged from recent duplications in a common ancestor ofScheffersoymcesandSpathasporato enable efficient xylose fermentation to ethanol. This study demonstrates the advantages of using metabolic simulations, omics data, bioinformatics, and enzymology to reverse engineer metabolism.


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