工业生物技术专刊序言

以生物催化和生物转化为核心的工业生物技术是实现社会和经济可持续发展的有效手段。本期专刊分别从基因工程、代谢工程与合成生物学、生理工程、发酵工程与生化工程、生物催化与生物转化、生物技术与方法等方面,介绍了我国在工业生物技术领域的最新研究进展。     

Opportunities for yeast metabolic engineering: Lessons from synthetic biology

Constant progress in genetic engineering has given rise to a number of promising areas of research that facilitated the expansion of industrial biotechnology. The field of metabolic engineering, which utilizes genetic tools to manipulate microbial metabolism to enhance the production of compounds of interest, has had a particularly strong impact by providing new platforms for chemical production. Recent developments in synthetic biology promise to expand the metabolic engineering toolbox further by creating novel biological components for pathway design. The present review addresses some of the recent advances in synthetic biology and how these have the potential to affect metabolic engineering in the yeast Saccharomyces cerevisiae. While S. cerevisiae for years has been a robust industrial organism and the target of multiple metabolic engineering trials, its potential for synthetic biology has remained relatively unexplored and further research in this field could strongly contribute to industrial biotechnology. This review also addresses are general considerations for pathway design, ranging from individual components to regulatory systems, overall pathway considerations and whole-organism engineering, with an emphasis on potential contributions of synthetic biology to these areas. Some examples of applications for yeast synthetic biology and metabolic engineering are also discussed.     

中国科学院工业生物技术发展路径

随着工程生物学、基因编辑等共性技术的快速发展,工业生物技术领域的颠覆式创新在低碳合成、未来食品、药物开发等工业生物技术领域不断取得颠覆式创新,支撑了生物产业高质量创新发展。工业生物技术正在为变革传统工业制造模式,构建碳中性工业制造路线形成重要科技支撑。本文从战略规划、创新机构、人才建设、基础研究、科技创新、产业推进等方面系统介绍了中国科学院在工业生物技术领域的整体安排、建制化研发与科技进展,并提出了加快工业生物技术发展的建议。     

The imminent role of protein engineering in synthetic biology

Protein engineering has for decades been a powerful tool in biotechnology for generating vast numbers of useful enzymes for industrial applications. Today, protein engineering has a crucial role in advancing the emerging field of synthetic biology, where metabolic engineering efforts alone are insufficient to maximize the full potential of synthetic biology. This article reviews the advancements in protein engineering techniques for improving biocatalytic properties to optimize engineered pathways in host systems, which are instrumental to achieve high titer production of target molecules. We also discuss the specific means by which protein engineering has improved metabolic engineering efforts and provide our assessment on its potential to continue to advance biology engineering as a whole.     

Impact of systems biology on metabolic engineering of Saccharomyces cerevisiae

Industrial biotechnology is a rapidly growing field. With the increasing shift towards a bio-based economy, there is rising demand for developing efficient cell factories that can produce fuels, chemicals, pharmaceuticals, materials, nutraceuticals, and even food ingredients. The yeast Saccharomyces cerevisiae is extremely well suited for this objective. As one of the most intensely studied eukaryotic model organisms, a rich density of knowledge detailing its genetics, biochemistry, physiology, and large-scale fermentation performance can be capitalized upon to enable a substantial increase in the industrial application of this yeast. Developments in genomics and high-throughput systems biology tools are enhancing one's ability to rapidly characterize cellular behaviour, which is valuable in the field of metabolic engineering where strain characterization is often the bottleneck in strain development programmes. Here, the impact of systems biology on metabolic engineering is reviewed and perspectives on the role of systems biology in the design of cell factories are given.     

Next‐Generation Industrial Biotechnology‐Transforming the Current Industrial Biotechnology into Competitive Processes

The chemical industry has made a contribution to modern society by providing cost‐competitive products for our daily use. However, it now faces a serious challenge regarding environmental pollutions and greenhouse gas emission. With the rapid development of molecular biology, biochemistry, and synthetic biology, industrial biotechnology has evolved to become more efficient for production of chemicals and materials. However, in contrast to chemical industries, current industrial biotechnology (CIB) is still not competitive for production of chemicals, materials, and biofuels due to their low efficiency and complicated sterilization processes as well as high‐energy consumption. It must be further developed into “next‐generation industrial biotechnology” (NGIB), which is low‐cost mixed substrates based on less freshwater consumption, energy‐saving, and long‐lasting open continuous intelligent processing, overcoming the shortcomings of CIB and transforming the CIB into competitive processes. Contamination‐resistant microorganism as chassis is the key to a successful NGIB, which requires resistance to microbial or phage contaminations, and available tools and methods for metabolic or synthetic biology engineering. This review proposes a list of contamination‐resistant bacteria and takes Halomonas spp. as an example for the production of a variety of products, including polyhydroxyalkanoates under open‐ and continuous‐processing conditions proposed for NGIB.     

Synthetic biology advances and applications in the biotechnology industry: a perspective

Synthetic biology is a logical extension of what has been called recombinant DNA (rDNA) technology or genetic engineering since the 1970s. As rDNA technology has been the driver for the development of a thriving biotechnology industry today, starting with the commercialization of biosynthetic human insulin in the early 1980s, synthetic biology has the potential to take the industry to new heights in the coming years. Synthetic biology advances have been driven by dramatic cost reductions in DNA sequencing and DNA synthesis; by the development of sophisticated tools for genome editing, such as CRISPR/Cas9; and by advances in informatics, computational tools, and infrastructure to facilitate and scale analysis and design. Synthetic biology approaches have already been applied to the metabolic engineering of microorganisms for the production of industrially important chemicals and for the engineering of human cells to treat medical disorders. It also shows great promise to accelerate the discovery and development of novel secondary metabolites from microorganisms through traditional, engineered, and combinatorial biosynthesis. We anticipate that synthetic biology will continue to have broadening impacts on the biotechnology industry to address ongoing issues of human health, world food supply, renewable energy, and industrial chemicals and enzymes.     

Recombinant antibodies: engineering and production in yeast and bacterial hosts

After the appearance of the first FDA-approved antibody 25 years ago, antibodies have become major therapeutic agents in the treatment of many human diseases, including cancer and infectious diseases, and the use of antibodies as therapeutic/diagnostic agents is expected to increase in the future. So far, a variety of strategies have been devised for engineering of these fascinating molecules to develop superior properties and functions. Recent progress in systems biology has provided more information about the structures and cellular networks of antibodies, and, in addition, recent development of biotechnology tools, particularly in regard to high-throughput screening, has made it possible to perform more intensive engineering on these substances. Based on a sound understanding and new technologies, antibodies are now being developed as more powerful drugs. In this review, we highlight the recent, significant progress that has been made in antibody engineering, with a particular focus on Fc engineering and glycoengineering for improved functions, and cellular engineering for enhanced production of antibodies in yeast and bacterial hosts.     

Protein design in systems metabolic engineering for industrial strain development

Accelerating the process of industrial bacterial host strain development, aimed at increasing productivity, generating new bio-products or utilizing alternative feedstocks, requires the integration of complementary approaches to manipulate cellular metabolism and regulatory networks. Systems metabolic engineering extends the concept of classical metabolic engineering to the systems level by incorporating the techniques used in systems biology and synthetic biology, and offers a framework for the development of the next generation of industrial strains. As one of the most useful tools of systems metabolic engineering, protein design allows us to design and optimize cellular metabolism at a molecular level. Here, we review the current strategies of protein design for engineering cellular synthetic pathways, metabolic control systems and signaling pathways, and highlight the challenges of this subfield within the context of systems metabolic engineering.     

工业生物技术中DNA合成发展现状及展望

DNA合成是生命科学领域的共性支撑技术和合成生物学的关键使能技术。以合成生物学为基础的工业生物技术持续快速发展,迫切需要更加便捷、经济、安全的DNA来源以满足其日益增长的大规模DNA合成需求。工业化DNA合成在通量、成本、速度等方面的优势日益凸显,有力推动了工业生物技术研发效率的提升和研发成本的下降。但是现有技术在生产过程中还存在着使用大量有机试剂、资源浪费等问题。随着DNA合成规模的持续快速提升,有毒化学品危害、成本负担、环境负担等问题日益突出。本文结合我们的工作实践,对工业生物技术中DNA合成需求、合成策略以及可持续发展面临的问题和解决方案研究进展进行探讨。     

The value of applying molecular biology tools in environmental engineering: Academic and industry perspective in the USA

The integration of molecular biology tools in environmental engineering is a challenge. We discuss our views on the following four critical issues: (i) faculty career development, (ii) tool standardization, (iii) teaching, and (iv) the application of molecular biology tools in practice. For (i), we suggest that administrators and faculty need to understand the special challenges inherent to research and teaching within this highly interdisciplinary area. Furthermore, we suggest preparing two white papers aimed at educating administrators in universities and agencies. For (ii), we conclude that, because molecular biology tools are still in a state of rapid development, proposing standards at this time is premature. In the future, standards for widely applied tools should be in an on-line, peer-reviewed format. Concerning (iii), we believe that molecular biology should be taught only to the degree needed to achieve program goals. For example, environmental engineering practitioners only need to know the vocabulary and basic concepts of molecular biology tools, not be experts at doing them hands on. To help engineering students gain the right level and type of information, learning modules should be developed for them. Finally, although engineering successes applying molecular biology tools are available (iv), the biggest value will come when the tools are fully integrated with practice. Therefore, we encourage the creation of a demonstration project to document the value of applying molecular biology tools in environmental engineering. This revised version was published online in June 2006 with corrections to the Cover Date.     

甲烷生物利用及嗜甲烷菌的工程改造

作为来源广泛、储量丰富的有机碳一气体,甲烷被认为是下一代工业生物技术中最具潜力的碳原料之一。嗜甲烷菌能够利用其体内的甲烷单加氧化酶,将甲烷作为唯一的碳源和能源进行生长和代谢,这为温室气体减排及其开发利用提供了新的策略。目前,嗜甲烷菌生物催化体系的相关研究已开展多年,随着系统生物学和合成生物学的快速发展,利用代谢工程合理改造嗜甲烷菌代谢途径以提高甲烷转化效率,已经实现了生物转化甲烷制备多种大宗化学品和生物燃料。本文详细讨论并介绍了嗜甲烷菌催化氧化甲烷的相关代谢途径、高效细胞工厂构建及部分化学品生物合成的最新研究进展,并对甲烷生物转化未来的发展方向和面临的技术挑战进行了讨论和展望。     

Synthetic biology tools for engineering Yarrowia lipolytica

The non-conventional oleaginous yeast Yarrowia lipolytica shows great industrial promise. It naturally produces certain compounds of interest but can also artificially generate non-native metabolites, thanks to an engineering process made possible by the significant expansion of a dedicated genetic toolbox. In this review, we present recently developed synthetic biology tools that facilitate the manipulation of Y. lipolytica, including 1) DNA assembly techniques, 2) DNA parts for constructing expression cassettes, 3) genome-editing techniques, and 4) computational tools.     

Engineering antibiotic production and overcoming bacterial resistance

Progress in DNA technology, analytical methods and computational tools is leading to new developments in synthetic biology and metabolic engineering, enabling new ways to produce molecules of industrial and therapeutic interest. Here, we review recent progress in both antibiotic production and strategies to counteract bacterial resistance to antibiotics. Advances in sequencing and cloning are increasingly enabling the characterization of antibiotic biosynthesis pathways, and new systematic methods for de novo biosynthetic pathway prediction are allowing the exploration of the metabolic chemical space beyond metabolic engineering. Moreover, we survey the computer-assisted design of modular assembly lines in polyketide synthases and non-ribosomal peptide synthases for the development of tailor-made antibiotics. Nowadays, production of novel antibiotic can be tranferred into any chosen chassis by optimizing a host factory through specific strain modifications. These advances in metabolic engineering and synthetic biology are leading to novel strategies for engineering antimicrobial agents with desired specificities.     

代谢工程30年专刊序言(2021)

代谢工程利用重组DNA技术、合成生物学、基因组编辑来改变生物体的细胞网络,包括代谢、基因调控和信号网络等.它可以实现加强包括化学品、燃料、化学原料药和其他生物技术产品等代谢物生产的目标,提升生物制造能力与效率.为了梳理和凝练代谢工程30年来的发展状况,《生物工程学报》特组织出版专刊,从代谢工程总体发展、共性技术以及以什...     

Metabolic engineering for the synthesis of polyesters: A 100-year journey from polyhydroxyalkanoates to non-natural microbial polyesters

As concerns increase regarding sustainable industries and environmental pollutions caused by the accumulation of non-degradable plastic wastes, bio-based polymers, particularly biodegradable plastics, have attracted considerable attention as potential candidates for solving these problems by substituting petroleum-based plastics. Among these candidates, polyhydroxyalkanoates (PHAs), natural polyesters that are synthesized and accumulated in a range of microorganisms, are considered as promising biopolymers since they have biocompatibility, biodegradability, and material properties similar to those of commodity plastics. Accordingly, substantial efforts have been made to gain a better understanding of mechanisms related to the biosynthesis and properties of PHAs and to develop natural and recombinant microorganisms that can efficiently produce PHAs comprising desired monomers with high titer and productivity for industrial applications.Recent advances in biotechnology, including those related to evolutionary engineering, synthetic biology, and systems biology, can provide efficient and effective tools and strategies that reduce time, labor, and costs to develop microbial platform strains that produce desired chemicals and materials. Adopting these technologies in a systematic manner has enabled microbial fermentative production of non-natural polyesters such as poly(lactate) [PLA], poly(lactate-co-glycolate) [PLGA], and even polyesters consisting of aromatic monomers from renewable biomass-derived carbohydrates, which can be widely used in current chemical industries.In this review, we present an overview of strain development for the production of various important natural PHAs, which will give the reader an insight into the recent advances and provide indicators for the future direction of engineering microorganisms as plastic cell factories. On the basis of our current understanding of PHA biosynthesis systems, we discuss recent advances in the approaches adopted for strain development in the production of non-natural polyesters, notably 2-hydroxycarboxylic acid-containing polymers, with particular reference to systems metabolic engineering strategies.