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Title: Strangers in a foreign land: ‘Yeastizing’ plant enzymes

Journal Article · · Microbial Biotechnology (Online)
 [1];  [2];  [1]; ORCiD logo [3]
  1. Horticultural Sciences Department University of Florida Gainesville Florida USA
  2. Department of Systems and Synthetic Metabolism Max Planck Institute of Molecular Plant Physiology Potsdam Germany, Department of Biochemistry Charité Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt‐Universität Berlin Germany
  3. Department of Biology University of Florida Gainesville Florida USA

Abstract Expressing plant metabolic pathways in microbial platforms is an efficient, cost‐effective solution for producing many desired plant compounds. As eukaryotic organisms, yeasts are often the preferred platform. However, expression of plant enzymes in a yeast frequently leads to failure because the enzymes are poorly adapted to the foreign yeast cellular environment. Here, we first summarize the current engineering approaches for optimizing performance of plant enzymes in yeast. A critical limitation of these approaches is that they are labour‐intensive and must be customized for each individual enzyme, which significantly hinders the establishment of plant pathways in cellular factories. In response to this challenge, we propose the development of a cost‐effective computational pipeline to redesign plant enzymes for better adaptation to the yeast cellular milieu. This proposition is underpinned by compelling evidence that plant and yeast enzymes exhibit distinct sequence features that are generalizable across enzyme families. Consequently, we introduce a data‐driven machine learning framework designed to extract ‘yeastizing’ rules from natural protein sequence variations, which can be broadly applied to all enzymes. Additionally, we discuss the potential to integrate the machine learning model into a full design‐build‐test cycle.

Research Organization:
Univ. of Florida, Gainesville, FL (United States)
Sponsoring Organization:
USDOE; USDOE Office of Science (SC), Basic Energy Sciences (BES)
Grant/Contract Number:
SC0020153
OSTI ID:
2439084
Journal Information:
Microbial Biotechnology (Online), Journal Name: Microbial Biotechnology (Online) Journal Issue: 9 Vol. 17; ISSN 1751-7915
Publisher:
Wiley-BlackwellCopyright Statement
Country of Publication:
United Kingdom
Language:
English

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