Unlocking the magic in mycelium: Using synthetic biology to optimize filamentous fungi for biomanufacturing and sustainability

Jo, Charles; Zhang, Jing; Tam, Jenny M.; Church, George M.; Khalil, Ahmad S.; Segrè, Daniel; Tang, Tzu-Chieh

doi:10.1016/j.mtbio.2023.100560

Title: Unlocking the magic in mycelium: Using synthetic biology to optimize filamentous fungi for biomanufacturing and sustainability

Journal Article · Sat Jan 21 00:00:00 EST 2023 · Materials Today Bio

DOI:https://doi.org/10.1016/j.mtbio.2023.100560· OSTI ID:1958544

^[1];

^[1]; Tam, Jenny M. ^[2];

^[2]; Khalil, Ahmad S. ^[3]; Segrè, Daniel ^[1];

^[2]

Boston Univ., MA (United States)
Harvard Medical School, Boston, MA (United States); Harvard Univ., Boston, MA (United States)
Boston Univ., MA (United States); Harvard Univ., Boston, MA (United States)

Filamentous fungi drive carbon and nutrient cycling across our global ecosystems, through its interactions with growing and decaying flora and their constituent microbiomes. The remarkable metabolic diversity, secretion ability, and fiber-like mycelial structure that have evolved in filamentous fungi have been increasingly exploited in commercial operations. The industrial potential of mycelial fermentation ranges from the discovery and bioproduction of enzymes and bioactive compounds, the decarbonization of food and material production, to environmental remediation and enhanced agricultural production. Despite its fundamental impact in ecology and biotechnology, molds and mushrooms have not, to-date, significantly intersected with synthetic biology in ways comparable to other industrial cell factories (e.g. Escherichia coli,Saccharomyces cerevisiae, and Komagataella phaffii). In this review, we summarize a suite of synthetic biology and computational tools for the mining, engineering and optimization of filamentous fungi as a bioproduction chassis. A combination of methods across genetic engineering, mutagenesis, experimental evolution, and computational modeling can be used to address strain development bottlenecks in established and emerging industries. These include slow mycelium growth rate, low production yields, non-optimal growth in alternative feedstocks, and difficulties in downstream purification. In the scope of biomanufacturing, we then detail previous efforts in improving key bottlenecks by targeting protein processing and secretion pathways, hyphae morphogenesis, and transcriptional control. Bringing synthetic biology practices into the hidden world of molds and mushrooms will serve to expand the limited panel of host organisms that allow for commercially-feasible and environmentally-sustainable bioproduction of enzymes, chemicals, therapeutics, foods, and materials of the future.

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Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division; National Science Foundation (NSF); National Institutes of Health (NIH); USDOD; Human Frontier Science Program (HFSP)

Grant/Contract Number:: AC02-05CH11231; FG02-02ER63445; MCB-2037995; 1R01AI171100-01; N00014-20-1-2825; RGP0060/2021

OSTI ID:: 1958544

Journal Information:: Materials Today Bio, Vol. 19; ISSN 2590-0064

Publisher:: ElsevierCopyright Statement

Country of Publication:: United States

Language:: English

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