AIと細菌の力を借りて発酵させたアルツハイマー病治療薬が現実に近づ(Alzheimer’s Drug Fermented With Help From AI and Bacteria Moves Closer to Reality)

ad

2024-03-14 テキサス大学オースチン校(UT Austin)

テキサス大学オースティン校の研究者は、人工知能とバイオセンサーを使用して、薬剤の迅速な開発の道を開拓しました。この革新的な方法では、遺伝子組み換えされた細菌を使用して、ガランタミンの化学前駆体を生成するプロセスが概説され、微生物を利用して医薬品を大量に発酵することが目指されています。この研究は、生産性の向上と薬物の製造コストの削減に寄与し、微生物を利用した製品の開発において人工知能が新たな可能性を拓くことを示しています。

<関連情報>

バイオセンサーと機械学習を援用したアマリリス科酵素のエンジニアリング Biosensor and machine learning-aided engineering of an amaryllidaceae enzyme

Simon d’Oelsnitz,Daniel J. Diaz,Wantae Kim,Daniel J. Acosta,Tyler L. Dangerfield,Mason W. Schechter,Matthew B. Minus,James R. Howard,Hannah Do,James M. Loy,Hal S. Alper,Y. Jessie Zhang & Andrew D. Ellington
Nature Communications  Published:07 March 2024
DOI:https://doi.org/10.1038/s41467-024-46356-y

AIと細菌の力を借りて発酵させたアルツハイマー病治療薬が現実に近づ(Alzheimer’s Drug Fermented With Help From AI and Bacteria Moves Closer to Reality)

Abstract

A major challenge to achieving industry-scale biomanufacturing of therapeutic alkaloids is the slow process of biocatalyst engineering. Amaryllidaceae alkaloids, such as the Alzheimer’s medication galantamine, are complex plant secondary metabolites with recognized therapeutic value. Due to their difficult synthesis they are regularly sourced by extraction and purification from the low-yielding daffodil Narcissus pseudonarcissus. Here, we propose an efficient biosensor-machine learning technology stack for biocatalyst development, which we apply to engineer an Amaryllidaceae enzyme in Escherichia coli. Directed evolution is used to develop a highly sensitive (EC50 = 20 μM) and specific biosensor for the key Amaryllidaceae alkaloid branchpoint 4’-O-methylnorbelladine. A structure-based residual neural network (MutComputeX) is subsequently developed and used to generate activity-enriched variants of a plant methyltransferase, which are rapidly screened with the biosensor. Functional enzyme variants are identified that yield a 60% improvement in product titer, 2-fold higher catalytic activity, and 3-fold lower off-product regioisomer formation. A solved crystal structure elucidates the mechanism behind key beneficial mutations.

有機化学・薬学
ad
ad
Follow
ad
タイトルとURLをコピーしました