Industrial biotechnology promises to revolutionize conventional chemical manufacturing in the years ahead, largely owing to the excellent progress in our ability to re-engineer cellular metabolism. However, most successes of metabolic engineering have been confined to over-producing natively synthesized metabolites in E. coli and S. cerevisiae. A major reason for this development has been the descent of metabolic engineering, particularly secondary metabolic engineering, to a collection of demonstrations rather than a systematic practice with generalizable tools. Synthetic biology, a more recent development, faces similar criticisms. Herein, we attempt to lay down a framework around which bioreaction engineering can systematize itself just like chemical reaction engineering. Central to this undertaking is a new approach to engineering secondary metabolism known as ‘multivariate modular metabolic engineering’ (MMME), whose novelty lies in its assessment and elimination of regulatory and pathway bottlenecks by re-defining the metabolic network as a collection of distinct modules. After introducing the core principles of MMME, we shall then present a number of recent developments in secondary metabolic engineering that could potentially serve as its facilitators. It is hoped that the ever-declining costs of de novo gene synthesis; the improved use of bioinformatic tools to mine, sort and analyze biological data; and the increasing sensitivity and sophistication of investigational tools will make the maturation of microbial metabolic engineering an autocatalytic process. Encouraged by these advances, research groups across the world would take up the challenge of secondary metabolite production in simple hosts with renewed vigor, thereby adding to the range of products synthesized using metabolic engineering.

工业生物技术有望在未来几年彻底改变传统的化学制造，这主要是由于我们重新设计细胞代谢的能力取得了巨大进步。然而，代谢工程的大多数成功仅限于在大肠杆菌和酿酒酵母中过度生产天然合成的代谢物. 这种发展的一个主要原因是代谢工程，特别是二级代谢工程，下降到一系列示范而不是具有可推广工具的系统实践。合成生物学是一项较新的发展，也面临着类似的批评。在此，我们试图建立一个框架，围绕该框架，生物反应工程可以像化学反应工程一样将其系统化。这项工作的核心是一种称为“多元模块化代谢工程”（MMME）的工程次级代谢的新方法，其新颖之处在于通过将代谢网络重新定义为不同模块的集合来评估和消除调节和途径瓶颈. 介绍完MMME的核心原理后，然后，我们将介绍可能作为其促进因素的次级代谢工程的一些最新进展。希望不断下降的成本从头基因合成；改进使用生物信息学工具来挖掘、分类和分析生物数据；研究工具的敏感性和复杂性的增加将使微生物代谢工程的成熟成为一种自催化过程。在这些进步的鼓舞下，世界各地的研究小组将以新的活力迎接在简单宿主中生产次级代谢物的挑战，从而增加使用代谢工程合成的产品范围。