{"id":7580,"date":"2026-01-26T05:50:57","date_gmt":"2026-01-26T05:50:57","guid":{"rendered":"https:\/\/fermentorchina.com\/?p=7580"},"modified":"2026-03-04T07:15:42","modified_gmt":"2026-03-04T07:15:42","slug":"penicillin-fermentation-experience-and-control","status":"publish","type":"post","link":"https:\/\/fermentorchina.com\/es\/penicillin-fermentation-experience-and-control\/","title":{"rendered":"Penicillin Fermentation Experience and Control"},"content":{"rendered":"

In the process of penicillin fermentation, the maximum biological yield is usually achieved by screening superior strains, regulating biological processes such as the metabolic development and growth of bacterial cells, and providing the optimal pH, temperature, as well as carbon and nitrogen sources in the fermentation broth.<\/p>\n

\"Penicillin\"<\/p>\n

These control conditions, along with various biological, physical-chemical and engineering environmental factors, exert a significant impact on the above processes. Therefore, studying the culture rules of bacterial cells, external control factors and methods to achieve optimal results has become an important task in fermentation engineering.<\/p>\n

\u4e00\u3001<\/strong>Descripci\u00f3n general<\/strong><\/h2>\n

The fermentation process is different from the chemical reaction process. It involves both the life processes of the growth, physiology and reproduction of biological cells, and the multi-enzyme reaction processes catalyzed by various enzymes secreted by microbial cells and their influencing factors. Thus, fermentation is a comprehensive application of the theories and technologies of microbiology, chemistry, engineering and other disciplines. Due to the complexity of the fermentation process, it is rather difficult to control, especially for the fermentation of secondary metabolites such as penicillin.<\/p>\n

\"SJA\"<\/p>\n

\u4e8c\u3001<\/strong>Applications and Main Production Process of Penicillin <\/strong><\/h2>\n

It\u00a0is an antibiotic extracted from the culture broth of Penicillium<\/i><\/em>\u00a0species, and it is the first antibiotic capable of treating human diseases. As a bactericidal agent, pcn\u00a0mainly acts on most Gram-positive bacteria, Gram-negative cocci, spirochetes and actinomycetes. It inhibits peptidoglycan synthesis, resulting in cell wall defects. Since susceptible bacteria have high internal osmotic pressure, water continuously infiltrates into the cells, causing the bacteria to swell, rupture and eventually die.<\/p>\n

The bactericidal characteristics of penicillin are as follows:<\/p>\n

    \n
  1. It has a strong effect on Gram-positive bacteria but a weak effect on Gram-negative bacteria. 2. It acts on bacteria in the logarithmic growth phase but has no effect on those in the stationary phase. 3. Because mammalian and fungal cells do not have cell walls, ithas low toxicity to humans and is ineffective against fungi. Production Process<\/i><\/em>: Lyophilized spores \u2192 Agar slant \u2192 Rice spores \u2192 Seed tank \u2192 Fermentation tank \u2192 Filtration \u2192 Butyl acetate extraction \u2192 Dehydration and decolorization \u2192 Crystallization \u2192 Crystal washing \u2192 Industrial salt \u2192 Mycelium \u2192 Comprehensive utilization. During the fermentation process, carbon sources, nitrogen sources, precursors and defoamers are added.<\/li>\n<\/ol>\n

    \u4e09\u3001Breeding of Penicillin-producing Strains <\/strong><\/h2>\n

    3.1 Selection of Original Strains <\/b><\/strong><\/p>\n

    Penicillin-producing strains are mainly Penicillium chrysogenum<\/i><\/em>\u00a051-20 and Penicillium notatum<\/i><\/em>. With Penicillium chrysogenum<\/i><\/em>\u00a0<\/i><\/em>51-20 as the parent strain, high-yield strains with a pcn\u00a0yield of over 30,000 u\/ml have been obtained through continuous mutagenesis. Penicillium<\/i><\/em>\u00a0exhibits certain morphological characteristics on solid media. At the initial stage of growth, spores swell first, germinate to form germ tubes that elongate rapidly, develop septa, reproduce to form hyphae, and then produce complex branches that interweave to form colonies.<\/p>\n

    Colonies may appear flat or highly wrinkled. On a medium with uniform nutrient distribution, colonies are generally circular, with edges that can be regular, serrated or fan-shaped. During development, conidiophores with sterigmata and metulae grow from aerial hyphae, and conidia are produced on the metulae, arranged in chains and shaped like a brush, which is called a penicillus.<\/p>\n

    Conidia are yellowish-green, green or blue, and turn yellowish-brown, reddish-brown or gray when aged. Conidia can be elliptical, cylindrical or spherical, and each strain has a specific conidial morphology that remains unchanged after multiple subcultures. Conidia are generally not produced in submerged culture.<\/p>\n

    3.2 Blocking Branch Metabolic Pathways <\/b><\/strong><\/p>\n

    When the primary metabolism and secondary metabolism of a strain follow branched pathways, auxotrophic mutants of primary metabolites can often increase the yield of corresponding secondary metabolites. For example, researchers obtained a leucine auxotrophic mutant through mutagenesis, which increased the pcn\u00a0yield by four times.<\/p>\n

    The biosynthesis of it\u00a0is subject to feedback inhibition by lysine, because lysine can inhibit or repress homocitrate synthesis. Therefore, by using lysine auxotrophic mutants and adding lysine to the medium, the pcn\u00a0yield can be significantly improved.<\/p>\n

    3.3 Breeding of Structural Analogue-resistant Mutants<\/b><\/strong><\/p>\n

    (1) Screening of Self-tolerant Mutants<\/p>\n

    Strains with different activities have varying degrees of self-tolerance, and high-yield strains can tolerate high concentrations of self-produced antibiotics. For this reason, self-produced antibiotics can be used to breed high-yield strains. For example, researchers screened a mutant strain that can tolerate 100,000 u\/ml of pcn\u00a0V, increasing the fermentation titer of pcn\u00a0to approximately 40,000 u\/ml. This type of self-tolerant mutant may have relieved feedback inhibition, greatly enhancing the activity of pcn\u00a0synthetase and thus promoting the synthesis of penicillin V.<\/p>\n