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Modeling coordinated enzymatic control of saccharification and fermentation by Clostridium thermocellum during consolidated bioprocessing of cellulose
Author(s) -
Ahamed Firnaaz,
Song HyunSeob,
Ho Yong Kuen
Publication year - 2021
Publication title -
biotechnology and bioengineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.136
H-Index - 189
eISSN - 1097-0290
pISSN - 0006-3592
DOI - 10.1002/bit.27705
Subject(s) - bioprocess , clostridium thermocellum , cellulase , cellobiose , cellulose , fermentation , population , biochemical engineering , chemistry , biochemistry , microbiology and biotechnology , biology , engineering , chemical engineering , demography , sociology
Abstract Consolidated bioprocessing (CBP) of cellulose is a cost‐effective route to produce valuable biochemicals by integrating saccharification, fermentation and cellulase synthesis in a single step. However, the lack of understanding of governing factors of interdependent saccharification and fermentation in CBP eludes reliable process optimization. Here, we propose a new framework that synergistically couples population balances (to simulate cellulose depolymerization) and cybernetic models (to model enzymatic regulation of fermentation) to enable improved understanding of CBP. The resulting framework, named the unified cybernetic‐population balance model (UC‐PBM), enables simulation of CBP driven by coordinated control of enzyme synthesis through closed‐loop interactions. UC‐PBM considers two key aspects in controlling CBP: (1) heterogeneity in cellulose properties and (2) cellular regulation of competing cell growth and cellulase secretion. In a case study on Clostridium thermocellum , UC‐PBM not only provides a decent fit with various exometabolomic data, but also reveals that: (i) growth‐decoupled cellulase‐secreting pathways are only activated during famine conditions to promote the production of growth substrates, and (ii) starting cellulose concentration has a strong influence on the overall flux distribution. Equipped with mechanisms of cellulose degradation and fermentative regulations, UC‐PBM is practical to explore phenotypic functions for primary evaluation of microorganisms’ potential for metabolic engineering and optimal design of bioprocess.