基于人工智能和计算生物学的合成生物学元件设计  

Design of synthetic biology components based on artificial intelligence and computational biology

作　　者：王晟 王泽琛 陈威华 陈珂 彭向达 欧发芬 郑良振 孙瑨原 沈涛 赵国屏 WANG Sheng;WANG Zechen;CHEN Weihua;CHEN Ke;PENG Xiangda;OU Fafen;ZHENG Liangzhen;SUN Jinyuan;SHEN Tao;ZHAO Guoping(Shanghai Zelixir Biotech Company Ltd.,Shanghai 200030,China;Shandong University,Jinan 250100,Shandong,China;Shenzhen Institute of Advanced Technology,Chinese Academey of Sciences,Shenzhen 518055,Guangdong,China;Institute of Microbiology,Chinese Academey of Sciences,Beijing 100101,China)

机构地区：[1]上海智峪生物科技有限公司,上海200030 [2]山东大学,山东济南250100 [3]中国科学院深圳先进技术研究院,广东深圳518055 [4]中国科学院微生物研究所,北京100101

出　　处：《合成生物学》2023年第3期422-443,共22页Synthetic Biology Journal

基　　金：中国科学院国际大科学计划培育专项(153D31KYSB20170121)。

摘　　要：合成生物学是按照一定的规律综合已有的信息设计和构建全新的生物元件、装置和系统,或者重新设计已有的天然生物系统。合成生物学的核心在于设计、改造、重建或制造生物元件、生物反应系统、代谢途径与过程,乃至创造具有生命活动能力的细胞和生物个体,为解决人类发展在环境、资源、能源等方面面临的若干重大挑战提供新技术方案。毫无疑问,从DNA重组到基因电路设计,合成生物学的发展为众多领域带来全新的解决方案,优良的催化与调控元件是设计高效、鲁棒的系统的基础。然而,合成生物学的元件通常是天然的生物大分子,其固有的复杂性限制了对其工程化改造,导致合成生物技术的潜力未能得到充分发掘。随着人工智能(artificial intelligence,AI)与计算生物学的兴起和发展,有望助力该技术更好地发挥其价值。本文主要介绍了基于AI与计算生物学的不同类型的元件设计,聚焦催化元件、调控元件、传感元件三类元件的设计和前沿进展以及生物元件改造在合成生物学研究领域中的应用方面的研究进展。The primary objective of synthetic biology is to conceptualize,engineer,and construct novel biological components,devices,and systems based on established principles and extant information or to reconfigure existing natural biological systems.The core concept of synthetic biology encompasses the design,modification,reconstruction,or fabrication of biological components,reaction systems,metabolic pathways and processes,and even the creation of cells and organisms with functions or living characteristics.This burgeoning field offers innovative technologies to address challenges with sustainable development in environment,resource,energy,and so on.Undeniably,synthetic biology has yielded significant progress in numerous fields,ranging from DNA recombination to gene circuit design,yet its full potential remains insufficiently explored,but the emergence and application of artificial intelligence(AI)definitely can facilitate the development of synthetic biology for more applications.From a synthetic biology perspective,essence for life is rooted in digitalization and designability.This article reviews current advances in computational biology,particularly AI for synthetic biology to be more efficient and effective,focusing on the development of biocatalysts,regulators,and sensors.De novo enzyme design has been successfully implemented by using Rosetta software,as AI exhibiting significant potential for generating innovative structures and protein sequences with diverse functions.Also,the reprogramming of natural enzymes for specific purposes is crucial for synthetic biology applications.By employing various force fields and sampling techniques,promiscuity and thermal stability can be modified to accommodate specific requirements rather than those with natural hosts.AI can be integrated into the life-cycle of synthetic biology through an active learning paradigm,which enables alterations in enzyme specificity,and demonstrates potential for accurately and rapidly predicting mutation effects,surpassing force-field-based m

关 键 词：人工智能 合成生物学 计算生物学 蛋白质设计 生物序列 

分 类 号：Q812[生物学—生物工程]