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Cheong, Seokjung

Publications and source records attributed to Cheong, Seokjung.

Engineering controllable alteration of malonyl-CoA levels to enhance polyketide production

Heterologous expression of polyketide synthase (PKS) genes in Escherichia coli has enabled the production of various valuable natural and synthetic products. However, the limited availability of malonyl-CoA (M-CoA) in E. coli remains a substantial impediment to high-titer polyketide production. Here we address this limitation by disrupting the native M-CoA biosynthetic pathway and introducing an orthogonal pathway comprising a malonate transporter and M-CoA ligase, enabling efficient M-CoA biosynthesis under malonate supplementation. This approach substantially increases M-CoA levels, enhancing fatty acid and polyketide titers while reducing the promiscuous activity of PKSs toward undesired acyl-CoA substrates. Subsequent adaptive laboratory evolution of these strains provides insights into M-CoA regulation and identifies mutations that further boost M-CoA and polyketide production. This strategy improves E. coli as a host for polyketide biosynthesis and advances understanding of M-CoA metabolism in microbial systems.

Klass, Sarah H↗

Hybrid biological-chemical strategy for converting polyethylene into a recyclable plastic monomer using engineered Corynebacterium glutamicum

Converting polyethylene (PE) into valuable materials, particularly ones that are better for the environment than the incumbent plastics, not only helps mitigate environmental issues caused by plastic waste but also alleviates the long-standing problem of microbial fermentation competing with food supplies. However, the inherent robustness of PE due to its strong carbon-carbon bonds and high molecular weight necessitates harsh decomposition conditions, resulting in diverse decomposition outcomes that present significant challenges for downstream applications, especially for bioconversion. In this study, we demonstrate a hybrid biological-chemical conversion process for PE, converting its decomposition products, namely short-chain diacids, into a monomer, β-keto-δ-lactone (BKDL), for highly recyclable polydiketoenimine plastics using engineered Corynebacterium glutamicum. Since BKDL synthesis requires a substantial supply of malonyl-CoA, we employed an alternative biosynthesis pathway that leverages C. glutamicum's natural proficiency in amino acid production. We optimized this pathway in vivo by minimizing carbon loss to CO2 and byproducts, improving the transporter system, and maximizing co-factor regeneration. Furthermore, we co-optimized the PE deconstruction process to produce predominantly C4 to C6 diacids and integrated three catabolic pathways into the engineered strain to enhance diacid utilization, maximizing the carbon conversion from PE. Finally, an engineered polyketide synthase was introduced into C. glutamicum to enable BKDL synthesis. This work demonstrates the potential of a chemo-biological hybrid strategy for recycling plastic waste, highlighting its promise in addressing environmental challenges and promoting sustainable materials.

Zhan, Chunjun↗

Biorenewable and circular polydiketoenamine plastics

Amid growing concerns over the human health and environmental impacts of plastic waste, the most promising solution would be to build a circular plastics economy where sustainability considerations dictate the full life cycle of plastics use including replacing petrochemicals with biorenewables. Here we show that by incorporating the polyketide triacetic acid lactone (TAL) in polydiketoenamines (PDK) we increase the working temperature of these circular plastics, opening the door wider to applications where circularity is urgently needed. By varying the number of carbons of TAL-derived monomers, both polymer properties and recycling efciency are afected. Simply using glucose as the main carbon source, we engineered a process for producing bioTAL under fed-batch fermentation. Furthermore, a systems analysis of this bioprocess under diferent scenarios quantifes the environmental and economic benefts of PDK plastics and the risks when implemented at an industrial scale, providing opportunities in biorenewable circularity.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗