Integration of metabolism and regulation reveals rapid adaptability to growth on non-native substrates.

Autor:	Trivedi VD; Department of Chemical & Biological Engineering, Tufts University, Medford, MA, USA., Sullivan SF; Department of Chemical & Biological Engineering, Tufts University, Medford, MA, USA., Choudhury D; Department of Chemical & Biological Engineering, Tufts University, Medford, MA, USA., Endalur Gopinarayanan V; Department of Chemical & Biological Engineering, Tufts University, Medford, MA, USA., Hart T; Department of Chemical & Biological Engineering, Tufts University, Medford, MA, USA., Nair NU; Department of Chemical & Biological Engineering, Tufts University, Medford, MA, USA. Electronic address: nikhil.nair@tufts.edu.
Jazyk:	angličtina
Zdroj:	Cell chemical biology [Cell Chem Biol] 2023 Sep 21; Vol. 30 (9), pp. 1135-1143.e5. Date of Electronic Publication: 2023 Jul 07.
DOI:	10.1016/j.chembiol.2023.06.009
Abstrakt:	Engineering synthetic heterotrophy is a key to the efficient bio-based valorization of renewable and waste substrates. Among these, engineering hemicellulosic pentose utilization has been well-explored in Saccharomyces cerevisiae (yeast) over several decades-yet the answer to what makes their utilization inherently recalcitrant remains elusive. Through implementation of a semi-synthetic regulon, we find that harmonizing cellular and engineering objectives are a key to obtaining highest growth rates and yields with minimal metabolic engineering effort. Concurrently, results indicate that "extrinsic" factors-specifically, upstream genes that direct flux of pentoses into central carbon metabolism-are rate-limiting. We also reveal that yeast metabolism is innately highly adaptable to rapid growth on non-native substrates and that systems metabolic engineering (i.e., functional genomics, network modeling, etc.) is largely unnecessary. Overall, this work provides an alternate, novel, holistic (and yet minimalistic) approach based on integrating non-native metabolic genes with a native regulon system. Competing Interests: Declaration of interests The authors declare no competing interest. (Copyright © 2023 Elsevier Ltd. All rights reserved.)
Databáze:	MEDLINE
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