With more than 20 years of development, Pichia pastoris system has been extensively used both on a lab and industrial scale. This review outlines the progress made on P. pastoris from aspects of protein expression, molecular engineering tools and methods, and biochemical production. This review also provides perspectives on the current challenges and future directions of this important system.
Bioengineering ; Industrial Microbiology ; Pichia

Industrial biotechnology promises to make a significant contribution in enabling the sustainable development, and need the solid support from its basic discipline. As the basis of industrial biotechnology, industrial biology is to study the basic laws and mechanisms of biological behavior in industrial environment and to solve the key scientific problems for understanding, designing and constructing the organisms adapted to the application of industrial environment. In order to comprehend the status of industrial biology, we published this special issue to review the progress and trends of industrial biology from the three aspects of industrial protein science, cell science and fermentation science, respectively, for laying the foundation for the development of industrial biotechnology.
Biotechnology ; Fermentation ; Industrial Microbiology

Industrial bioprocess is a complex systematic process and bio-manufacturing can be realized on the basis of understanding the metabolism process of living cells. In this article, the multi-scale optimization principle and practice of industrial fermentation process are reviewed, including multi-scale optimizing theory and equipment, on-line sensing technology for cellular macroscopic metabolism, and correlated analysis of physiological parameters. Furthermore, intelligent control of industrial bioprocess is further addressed, in terms of new sensing technology for intracellular physiological metabolism, big database establishment and data depth calculation, intelligent decision.
Bioreactors ; Biotechnology ; Fermentation ; Industrial Microbiology

In the last few years, high-throughput (or 'next-generation') sequencing technologies have delivered a step change in our ability to sequence genomes, whether human or bacterial. Further comparative genome analysis enables us to reveal detailed knowledge of genetics or physiology of industrial important strains obtained in laboratory, to analyze genotype-phenotype correlations of mutants with improved performance. Based on identified key mutations or mutation combinations, Inverse Metabolic Engineering (IME) can be performed by using accurate genetic modification system. Recently, IME has been successfully used for strain improvement and has become a research hotspot, including improving substrate utilization, engineering the robustness of industrial microbes and enhancing production of bio-based products. Here, we describe recent advances in research methods of IME, with an emphasis on characterization of genotype-phenotype and the latest advances and application of IME. Possible directions and challenges for further development of IME are also discussed.
Industrial Microbiology ; trends ; Metabolic Engineering ; trends ; Mutation

Polymalic acid, known as a bioactive material, is completely biodegradable, and has far reaching application potential in medical field. Combined with our own findings, we summarized advances in polymalic acid metabolism, microbial fermentation synthesis, and application research in the medical field. Finally, prospect for further research was addressed.
Fermentation ; Industrial Microbiology ; Malates ; chemistry ; Polymers ; chemistry

Industrial fermentation is the basic operation unit of industrial biotechnology in large-scale production. Mathematical simulation of microbial cells and their reactors will help deepen the understanding of microorganisms and fermentation processes, and will also provide solutions for the construction of new synthetic organisms. In this paper, the characteristics of industrial fermentation system, the development of mathematical simulation, the classification, characteristics and functions of mathematical models are described in depth, and the development trend of whole fermentation system simulation is prospected.
Biotechnology ; Fermentation ; Industrial Microbiology ; Models, Biological

Different types of acids from fermentation environment or industrial microorganisms exist during fermentation process. Acids may inhibit growth and metabolism of industrial strains, namely acid stress. The tolerance mechanisms of acid stress include regulation of intracellular proton concentration, protection and restoration of intracellular macromolecules, changes in cell membrane composition and acid stress response at whole cell level. Screening and modification methods have been applied to improve acid-stress tolerance of industrial strains for decades. In this review, we provide insights into acid-stress tolerance of industrial microorganisms and address the modification of microbial pathways to improve acid-stress tolerance.
Acids ; chemistry ; Fermentation ; Hydrogen-Ion Concentration ; Industrial Microbiology ; Metabolic Engineering

Pinocembrin, belonging to flavanons, was isolated from various plants. Pinocembrin has a variety of pharmacological activities, such as neuroprotective effect, antimicrobial activity, and antioxidant efficacy. Pinocembrin was approved as class I drugs to its phase II clinical trial by CFDA in 2009, mainly used for the treatment of ischemic stroke. As a promising compound, the manufacturing technologies of pinocembrin, including chemical synthesis, extraction from plant and synthetic biology, have attracted many attentions. Compared with the first two technologies, synthetic biology has many advantages, such as environment-friendly and low-cost. Construction of biosynthetic pathway in microorganism offers promising results for large scale pinocembrin production by fermentation after taking lots of effective strategies. This article reviews some of recent strategies in microorganisms to improve the yield, with focus on the selection of appropriate the key enzyme sources, the supply of precursors and cofactors by microorganisms, the choice of substance and the level of the key enzyme expression.
Biosynthetic Pathways ; Fermentation ; Flavanones ; biosynthesis ; Industrial Microbiology ; Plants ; Synthetic Biology

Genome editing is defined as highly-effective and precise modification of cellular genome in a large scale. In recent years, such genome-editing methods have been rapidly developed in the field of industrial strain improvement. The quickly-updating methods thoroughly change the old mode of inefficient genetic modification, which is "one modification, one selection marker, and one target site". Highly-effective modification mode in genome editing have been developed including simultaneous modification of multiplex genes, highly-effective insertion, replacement, and deletion of target genes in the genome scale, cut-paste of a large DNA fragment. These new tools for microbial genome editing will certainly be applied widely, and increase the efficiency of industrial strain improvement, and promote the revolution of traditional fermentation industry and rapid development of novel industrial biotechnology like production of biofuel and biomaterial. The technological principle of these genome-editing methods and their applications were summarized in this review, which can benefit engineering and construction of industrial microorganism.
Biotechnology ; Fermentation ; Genetic Engineering ; methods ; Genome, Microbial ; Industrial Microbiology

Filamentous fungi are widely used in industrial fermentation. Particular fungal morphology acts as a critical index for a successful fermentation. To break the bottleneck of morphological analysis, we have developed a reliable method for fungal morphological analysis. By this method, we can prepare hundreds of pellet samples simultaneously and obtain quantitative morphological information at large scale quickly. This method can largely increase the accuracy and reliability of morphological analysis result. Based on that, the studies of Aspergillus niger morphology under different oxygen supply conditions and shear rate conditions were carried out. As a result, the morphological responding patterns of A. niger morphology to these conditions were quantitatively demonstrated, which laid a solid foundation for the further scale-up.
Aspergillus niger ; cytology ; Fermentation ; Industrial Microbiology ; Reproducibility of Results