Penicillium Chrysogenium is a very high yielding strain, this is why it is widely used in the production of Penicillin G (Benzylpenicillin). This is achieved by introducing spores of strain to appropriate environment so that spores can germinate and form mycelium which is the vegetative part of the mold, then microorganism is allowed to grow and reproduce, until stationary phase, it is then starting to produce penicillin.
Penicillin has been one of the best Discoveries of Medical Science which literally changed the face of Medical Science. Life before Penicillin & Life after penicillin has shown tremendous difference in Life Span of Humans as well as other mammals .
Alexander Fleming showed the world THE POTENCY of ANTIBIOTICS ....
Penicillin has been one of the best Discoveries of Medical Science which literally changed the face of Medical Science. Life before Penicillin & Life after penicillin has shown tremendous difference in Life Span of Humans as well as other mammals .
Alexander Fleming showed the world THE POTENCY of ANTIBIOTICS ....
Introduction :
Antibiotics are antimicrobial agents produced naturally by other microbes (usually fungi or bacteria)
The first antibiotic was discovered in 1896 by Ernest Duchesne and in 1928 "rediscovered" by Alexander Fleming from the filamentous fungus Penicilium notatum.
The antibiotic substance, named penicillin, was not purified until the 1940s (by Florey and Chain), just in time to be used at the end of the second world war.
Penicillin was the first important commercial product produced by an aerobic, submerged fermentation
This presentation is about what exactly is penicillin and how it was discovered along with its industrial production process from fermentors until yield.
Explanation on the industrial production of penicillin covering the history, fermentors, specific conditions required for penicillin production, how to increase yield amongst others.
Penicillin is a antibiotic having β-lactum thiazolidine ring.
Penicillin G is the starting material for 6-amino penicillanic acid which is the key intermediate in the production of wide range of semi synthetic penicillins.
Mold used for the production of penicillin is Penicillium chrysogenum
Penicillin is a antibiotic having β-lactum thiazolidine ring.
Penicillin G is the starting material for 6-amino penicillanic acid which is the key intermediate in the production of wide range of semi synthetic penicillins.
Mold used for the production of penicillin is Penicillium chrysogenum
types of fermentation
Basically ,there are two methods of preparation of penicillin by fermentation:
Surface Culture Method:
In this method mold is grown on the surface of shallow layers of the fermentation medium.
Submerged Culture Method:
In this method mold is grown submerged in the fermentation medium.
master stock culture
It can be preserved by
Freeze drying
Fixing on soil sand mixtures
Storage under liquid nitrogen
Second method is the best method
Industrial production of penicillin.ppt523JoyceAngel
Industrial productioon of penicillin.
penicillin is a group of antibiotic obtained from fungi mold Penicillium notatum (in begining) ,Penicillium chrysogenum (used in present days due to high yield) and P. rubens. Most penicillins in clinical use are synthesised by P. chrysogenum .
First discovered Antibiotic.
Discovered by Alexander Fleming in 1928.
Penicillin is a group of antibiotics which includes Penicillin G, Penicillin V, Amoxillin, Ampicillin, Methicillin, Oxacillin, Dicloxallin, Carbenicillin, Propicillin and Benzathine penicillin.
Narrow spectrum antibiotic
Cell wall inhibitor – Inhibits peptidoglycan synthesis.
More effective against Gram positive bacteria.
5 steps in penicillin production
1.Selection of microorganism
2.Selection of raw materials
3. Preparation of inoculum
4. Fermentation process
5. Product recovery
streptomycin production, uses, disadvantages , medium, inoculum preparation, commercial production, harvest and recovery process, biosynthetic pathway from glucose to streptomycin, flow sheet of streptomycin production by submerged culture method, chemical structure of streptomycin,
which functional unit have antibiotic activity?
Introduction :
Antibiotics are antimicrobial agents produced naturally by other microbes (usually fungi or bacteria)
The first antibiotic was discovered in 1896 by Ernest Duchesne and in 1928 "rediscovered" by Alexander Fleming from the filamentous fungus Penicilium notatum.
The antibiotic substance, named penicillin, was not purified until the 1940s (by Florey and Chain), just in time to be used at the end of the second world war.
Penicillin was the first important commercial product produced by an aerobic, submerged fermentation
This presentation is about what exactly is penicillin and how it was discovered along with its industrial production process from fermentors until yield.
Explanation on the industrial production of penicillin covering the history, fermentors, specific conditions required for penicillin production, how to increase yield amongst others.
Penicillin is a antibiotic having β-lactum thiazolidine ring.
Penicillin G is the starting material for 6-amino penicillanic acid which is the key intermediate in the production of wide range of semi synthetic penicillins.
Mold used for the production of penicillin is Penicillium chrysogenum
Penicillin is a antibiotic having β-lactum thiazolidine ring.
Penicillin G is the starting material for 6-amino penicillanic acid which is the key intermediate in the production of wide range of semi synthetic penicillins.
Mold used for the production of penicillin is Penicillium chrysogenum
types of fermentation
Basically ,there are two methods of preparation of penicillin by fermentation:
Surface Culture Method:
In this method mold is grown on the surface of shallow layers of the fermentation medium.
Submerged Culture Method:
In this method mold is grown submerged in the fermentation medium.
master stock culture
It can be preserved by
Freeze drying
Fixing on soil sand mixtures
Storage under liquid nitrogen
Second method is the best method
Industrial production of penicillin.ppt523JoyceAngel
Industrial productioon of penicillin.
penicillin is a group of antibiotic obtained from fungi mold Penicillium notatum (in begining) ,Penicillium chrysogenum (used in present days due to high yield) and P. rubens. Most penicillins in clinical use are synthesised by P. chrysogenum .
First discovered Antibiotic.
Discovered by Alexander Fleming in 1928.
Penicillin is a group of antibiotics which includes Penicillin G, Penicillin V, Amoxillin, Ampicillin, Methicillin, Oxacillin, Dicloxallin, Carbenicillin, Propicillin and Benzathine penicillin.
Narrow spectrum antibiotic
Cell wall inhibitor – Inhibits peptidoglycan synthesis.
More effective against Gram positive bacteria.
5 steps in penicillin production
1.Selection of microorganism
2.Selection of raw materials
3. Preparation of inoculum
4. Fermentation process
5. Product recovery
streptomycin production, uses, disadvantages , medium, inoculum preparation, commercial production, harvest and recovery process, biosynthetic pathway from glucose to streptomycin, flow sheet of streptomycin production by submerged culture method, chemical structure of streptomycin,
which functional unit have antibiotic activity?
A broad module on industrial microbiology is summarized with pictures .It includes the production of vitamins,vaccine ,alcohol,vinegar,steroids,amino acids ,antibiotics .it also includes the general idea on history ,media,equipment,fermentation,procedure ,uses of industrial microbiology .The production of wine,beer and vinegar are mine core interest .Hope may help ....Thank you .
This PPT will provide the basic idea of Fermentation technology and it's use. The reference book is 'Pharmaceutical Biotechnology' by Giriraj Kulkarni.
It is about information about well known pharmaceutical industry in Pune , which also includes production of penicillin and Streptomycin which is helpful for biotechnology students
BOTECHNOLOGY IS CHALLENGING SUBJECT TO TEACH AND UNDERSTAND ALSO .....THEIR INTERESTING PART IS TO LEARN ABOUT PRODUCTION OF CITRIC ACID , PENICILLIN, GLUTAMIC ACID , GRISIOFULVIN , VITAMIN B 12
UiPath Test Automation using UiPath Test Suite series, part 3DianaGray10
Welcome to UiPath Test Automation using UiPath Test Suite series part 3. In this session, we will cover desktop automation along with UI automation.
Topics covered:
UI automation Introduction,
UI automation Sample
Desktop automation flow
Pradeep Chinnala, Senior Consultant Automation Developer @WonderBotz and UiPath MVP
Deepak Rai, Automation Practice Lead, Boundaryless Group and UiPath MVP
Epistemic Interaction - tuning interfaces to provide information for AI supportAlan Dix
Paper presented at SYNERGY workshop at AVI 2024, Genoa, Italy. 3rd June 2024
https://alandix.com/academic/papers/synergy2024-epistemic/
As machine learning integrates deeper into human-computer interactions, the concept of epistemic interaction emerges, aiming to refine these interactions to enhance system adaptability. This approach encourages minor, intentional adjustments in user behaviour to enrich the data available for system learning. This paper introduces epistemic interaction within the context of human-system communication, illustrating how deliberate interaction design can improve system understanding and adaptation. Through concrete examples, we demonstrate the potential of epistemic interaction to significantly advance human-computer interaction by leveraging intuitive human communication strategies to inform system design and functionality, offering a novel pathway for enriching user-system engagements.
The Art of the Pitch: WordPress Relationships and SalesLaura Byrne
Clients don’t know what they don’t know. What web solutions are right for them? How does WordPress come into the picture? How do you make sure you understand scope and timeline? What do you do if sometime changes?
All these questions and more will be explored as we talk about matching clients’ needs with what your agency offers without pulling teeth or pulling your hair out. Practical tips, and strategies for successful relationship building that leads to closing the deal.
Software Delivery At the Speed of AI: Inflectra Invests In AI-Powered QualityInflectra
In this insightful webinar, Inflectra explores how artificial intelligence (AI) is transforming software development and testing. Discover how AI-powered tools are revolutionizing every stage of the software development lifecycle (SDLC), from design and prototyping to testing, deployment, and monitoring.
Learn about:
• The Future of Testing: How AI is shifting testing towards verification, analysis, and higher-level skills, while reducing repetitive tasks.
• Test Automation: How AI-powered test case generation, optimization, and self-healing tests are making testing more efficient and effective.
• Visual Testing: Explore the emerging capabilities of AI in visual testing and how it's set to revolutionize UI verification.
• Inflectra's AI Solutions: See demonstrations of Inflectra's cutting-edge AI tools like the ChatGPT plugin and Azure Open AI platform, designed to streamline your testing process.
Whether you're a developer, tester, or QA professional, this webinar will give you valuable insights into how AI is shaping the future of software delivery.
Securing your Kubernetes cluster_ a step-by-step guide to success !KatiaHIMEUR1
Today, after several years of existence, an extremely active community and an ultra-dynamic ecosystem, Kubernetes has established itself as the de facto standard in container orchestration. Thanks to a wide range of managed services, it has never been so easy to set up a ready-to-use Kubernetes cluster.
However, this ease of use means that the subject of security in Kubernetes is often left for later, or even neglected. This exposes companies to significant risks.
In this talk, I'll show you step-by-step how to secure your Kubernetes cluster for greater peace of mind and reliability.
Elevating Tactical DDD Patterns Through Object CalisthenicsDorra BARTAGUIZ
After immersing yourself in the blue book and its red counterpart, attending DDD-focused conferences, and applying tactical patterns, you're left with a crucial question: How do I ensure my design is effective? Tactical patterns within Domain-Driven Design (DDD) serve as guiding principles for creating clear and manageable domain models. However, achieving success with these patterns requires additional guidance. Interestingly, we've observed that a set of constraints initially designed for training purposes remarkably aligns with effective pattern implementation, offering a more ‘mechanical’ approach. Let's explore together how Object Calisthenics can elevate the design of your tactical DDD patterns, offering concrete help for those venturing into DDD for the first time!
DevOps and Testing slides at DASA ConnectKari Kakkonen
My and Rik Marselis slides at 30.5.2024 DASA Connect conference. We discuss about what is testing, then what is agile testing and finally what is Testing in DevOps. Finally we had lovely workshop with the participants trying to find out different ways to think about quality and testing in different parts of the DevOps infinity loop.
UiPath Test Automation using UiPath Test Suite series, part 4DianaGray10
Welcome to UiPath Test Automation using UiPath Test Suite series part 4. In this session, we will cover Test Manager overview along with SAP heatmap.
The UiPath Test Manager overview with SAP heatmap webinar offers a concise yet comprehensive exploration of the role of a Test Manager within SAP environments, coupled with the utilization of heatmaps for effective testing strategies.
Participants will gain insights into the responsibilities, challenges, and best practices associated with test management in SAP projects. Additionally, the webinar delves into the significance of heatmaps as a visual aid for identifying testing priorities, areas of risk, and resource allocation within SAP landscapes. Through this session, attendees can expect to enhance their understanding of test management principles while learning practical approaches to optimize testing processes in SAP environments using heatmap visualization techniques
What will you get from this session?
1. Insights into SAP testing best practices
2. Heatmap utilization for testing
3. Optimization of testing processes
4. Demo
Topics covered:
Execution from the test manager
Orchestrator execution result
Defect reporting
SAP heatmap example with demo
Speaker:
Deepak Rai, Automation Practice Lead, Boundaryless Group and UiPath MVP
Generating a custom Ruby SDK for your web service or Rails API using Smithyg2nightmarescribd
Have you ever wanted a Ruby client API to communicate with your web service? Smithy is a protocol-agnostic language for defining services and SDKs. Smithy Ruby is an implementation of Smithy that generates a Ruby SDK using a Smithy model. In this talk, we will explore Smithy and Smithy Ruby to learn how to generate custom feature-rich SDKs that can communicate with any web service, such as a Rails JSON API.
Encryption in Microsoft 365 - ExpertsLive Netherlands 2024Albert Hoitingh
In this session I delve into the encryption technology used in Microsoft 365 and Microsoft Purview. Including the concepts of Customer Key and Double Key Encryption.
Key Trends Shaping the Future of Infrastructure.pdfCheryl Hung
Keynote at DIGIT West Expo, Glasgow on 29 May 2024.
Cheryl Hung, ochery.com
Sr Director, Infrastructure Ecosystem, Arm.
The key trends across hardware, cloud and open-source; exploring how these areas are likely to mature and develop over the short and long-term, and then considering how organisations can position themselves to adapt and thrive.
GraphRAG is All You need? LLM & Knowledge GraphGuy Korland
Guy Korland, CEO and Co-founder of FalkorDB, will review two articles on the integration of language models with knowledge graphs.
1. Unifying Large Language Models and Knowledge Graphs: A Roadmap.
https://arxiv.org/abs/2306.08302
2. Microsoft Research's GraphRAG paper and a review paper on various uses of knowledge graphs:
https://www.microsoft.com/en-us/research/blog/graphrag-unlocking-llm-discovery-on-narrative-private-data/
2. Antibiotics
◦ The term antibiotic has been defined by Selman Waksman as being an organic
compound produced by one microorganism that inhibits the growth of or kills a
group of harmful microorganisms (Bacteria).
◦ These enter and stick to important parts (think of targets) of the bacterial cell, and
interfere with its ability to survive and multiply [1].
If the bacteria are susceptible to the antibiotic, then they will stop growing or simply
die.
◦ These important parts include:
◦ Proteins/sugars in the bacterial wall.
◦ Important enzymes that make new bacterial DNA or proteins[2].
4. First Naturally-occuring Antibiotic
◦ Fleming was already well known upon
his return from a long holiday in September
1928, he noted that one petri dish contained
colonies of staphylococcus bacteria except for
clear area contaminated with a fungus that
appeared to inhibit bacterial growth. The
mold was found to be penicillium notatum[3].
6. Staphylococcus Aureus
◦ Staphylococcus is a genus of Gram-positive bacteria. Under the microscope, they
appear spherical, and form in grape-like clusters. It can cause scarlet fever, pneumonia
or sepsis [3].
Figure 2: illustrations of staphylococci bacteria and its arrangement.
7. General Structure
of Penicillin
Penicillin is not a single compound but a
group of closely related compounds, all
with the same basic ring-like structure (a
β-lactam) derived from two amino acids
(valine and cysteine) via a tripeptide
intermediate.
The third amino acid of this tripeptide is
replaced by an acyl group (R) and the
nature of this acyl group produces
specific properties on different types of
penicillin.[4].
Figure 3: Shows the chemical Structure of Penicillins
group.
9. Types of β-lactam antibiotics:
◦ Penicillins are either :
1. Natural penicillin.
2. Semisynthetic penicillin.
10. Penicillin Production
Aim:
To provide sterile, controlled and homogeneous environment in which the fermentation can carryout
in a manner that is safe and practical and which optimizes the Penicillin production for ultimate use.
UPSTREAM PROCESSING :
It the steps taken that lead to the synthesis of a product.
Upstream includes the development and production.
DOWNSTREAM PROCESSING :
The extraction and purification of a product from fermentation.
11. Step 1: Inoculum Preparation.
◦ Inoculum: A small amount of material containing bacteria, viruses,
or other microorganisms that is used to start a culture[5].
◦ Out of various species of the fungus Penicillium, mainly two species are used in
the fermentation:
◦ These are P. notatum & P. chrysogenum but P. chrysogenum is high yielding
strain and therefore most widely used as production strain[6].
12. Penicillium Chrysogenum
◦ It is able to synthesize penicillins with specific hydrophobic side chains when the
appropriate precursor is fed to the production medium.
◦ PA appears to be the best precursor, but the phenyl group can be substituted or
replaced by other ring systems.
◦ penicillin G, penicillin V, or penicillin O. In the absence of an exogenous side
chain precursor, P. chrysogenum produces mainly 6-aminopenicillanic acid.
13. Myceilium
◦ The mycelium is well developed and
copiously branched.
◦ It is composed of colourless, slender,
tubular, branched and septate hyphae.
◦ The hyphae run in all directions and
become intertwined with one another
to form a loose network of hyphae
constituting the mycelium.
◦ Myceilium is the vegitative part of
the mold [7].
Figure 5: Shows the Mycelium structure and how
spores germinate.
14. Secondary Metabolite
◦ penicillin is a secondary metabolite,
so is only produced in the stationary
phase.
◦ Note that: it is only produced in times
of stress when resources are low and
the organism must produce these
compounds to kill off its competitors
to allow it to surviveFigure 6: Variation in number of cells of
Microorganism during time in days.
15. Figure 7: Difference between Primary metabolite (Alcohol Fermentation and Secondry Metabolite
(Penicillin fermentation).
16. Maintenance of Strain.
◦ The production strain should be carefully maintained because
appropriate maintenance and production of reliable pure cultures with desirable
quality is a key operation.
◦ The Microorganism was maintained as lyophilized spore suspension until usage.
17. Step 2: Nutrients Sterilization.
◦ Throughout the fermentation industry, heating using steam is widely used as a
sterilization method, since it is reliable and easy to control.
◦ Sterilization of culture is necessary to prevent contamination.
18. Step 3: Inoculum Build-up.
◦ Here the chief purpose is to develop a pure inoculum in an adequate amount
and in the fast growing phase for the production stage fermenter.
1. Starter culture is transferred into agar-plate to allow growth.
When spores are placed on a vegetative media , the spores start to germinate and form
myceilia.
2. after growth on agar-plate, Cultures were incubated for approximately 70 h in
a rotary shaker at 200 rpm and 25C, to improve oxygen diffusion.
3. two growth stages (2 days incubation)are allowed upon transfer into seed
fermenter.
19. Step 4: Seed Fermenters.
◦ Initial stages of fermentation are designed for considerable microbial growth and the
can be distiguished from main Bioreactors by several factors; these are:
1. Smaller in size than the main fermenters approx. 2 Liter capacity
2. Made of stainless steel.
3. Equipped with agitators, which allow continuous mixing of growth medium.
4. Provided with pump to deliver sterilized, filtered air.
◦ Must contain all the nutrients including Growth factors.
◦ After about 24-28 hours, the content of the seed tanks is transferred to fermentation
tank.
20. Step 5: Bioreactor Set-up.
Fed-Batch culture: to feed a batch by controlled addition of a carbon source
and/or other nutrients, resulting in a fed-batch culture.
Air-lift Bioreactor:
◦ Advantages:
considerably higher volumetric and specific productivities since the phenotype
of the cell is under better control[8].
21. Bioreactor Specifications
Table 1: The different parameters in a bioreactor.
Different
Aspects
Procedure
Volume 300-500m3, made from stainless steel.
agitation provided at a rate of 100 to 300 rpm.
Temperature controlled by using cooling coils.
Parameters
Monitoring
Dissolved oxygen and other parameters should be continuously controlled,
this is achieved by the withdrawal of small volumes of broth in the fermenter.
Aeration Vigorous supplied from the bottom of fermenters by ring or tube sparges.
Common
Problems
Due to the high viscosity of the broth, oxygen transfer is a major
problem in penicillin fermentations.
22. Broth preparation:
Raw Materials
Raw materials are primary requirement to design the fermentation broth for
antibiotic production.
◦ Fermentation broth contains all the necessary elements required for the
proliferation of the microorganisms.
23. Carbon Source:
Lactose acts as a very satisfactory carbon compound when it is used as a food
source for the microorganism. with slow feeding rate.
◦ Corn oil supplemented with lactose results in fast production of highly
concentrated penicillin.
◦ Glucose, fructose, galactose and etc. Are easily utilized carbon sources reduce
penicillin titer while the titer in lactose is high.
◦Note: In inoculum medium lactose is generally absent because it induces penicillin
production and retarding the growth of production strain.
24. Nitrogen Source:
◦ Another essential compound for metabolism of organisms is nitrogen.
◦ We use Corn steep liquor (CSL), since it results in higher penicillin yields as
compared to the other nitrogen sources. Some compounds in CSL are
converted to phenylacetic acid or other side-chain precursors.
◦ Cottonseed flour or soybean meal may also be used as nitrogen sources; however,
they are more expensive than CSL [9].
25. Ammonium Source.
◦ Continuous addition of ammonium sulfate to keep the ammonium concentration
around 250–300 mg/L is required for continued synthesis of penicillin and
to avoid lysis of the mycelium.
◦ The omission of ammonium nitrate decreased the penicillin activity in the
original fermentation medium (Table I).
◦ This result agrees with the findings of [10] they reported that ammonium
nitrogen is a limiting factor in penicillin production.
26. Mineral Source:
◦Additionally, some minerals are necessary for the proper growth of these
organisms. are included.
◦ These elements include phosphorus, sulfur, magnesium, zinc, iron, and copper
which generally added in the form of water soluble salts.
◦For example:
◦However, the pH at the end of the fermentation period is slightly lower, when
low concentrations of calcium carbonate were used[10]
27. AntiFoam Agents:
Anti-foaming agents such as lard oil to reduce foam formation.
Disadvantages of Foaming:
1. Reduce process productivity since bursting bubbles can damage proteins[11],
2. Can result in loss of sterility if the foam escapes the bioreactor[13].
3. leads to over-pressure if a foam-out blocks an exit filter.
28. Precursors.
◦ Certain precursors of the penicillin side chain need to be added into the
fermentation medium.
◦ This constitutes a major cost item. Penicillin G requires 0.47g sodium phenylacetate.
◦ the precursor must be added repeatedly in small amounts during the fermentation:
why?
In order to avoid toxic effects.
◦ The Phenylacetic acid appears to be the best precursor, but it can be substituted or
replaced by other ring systems[14]. it is transported across the plasma membrane by
free diffusion into myceilium.
29. Table 2: Constitutes of penicillin G fermentation broth.
Media Percentage%
Lactose 3-4
Glucose 10
Corn steep liquor 4
CaCO3 1
Antifoam 0.25-0.5
Phenyl acetic acid 0.5
KH2PO4 0.4
30. Step 6: Production.
Table 3: Parameters monitored in penicillin fermentation.
Parameter Status
PH Around 6.5-7
Temperature 26°C to 28°C
Aeration continuous stream of sterilized air is pumped
into it
Agitation baffles which allow constant agitation
31. Inside the Bioreactor.
First phase-
growth of the mycelium occurs, yield of antibiotic is quite low.Lactic acid present in corn steep liquor is
utilized at the maximum rate by the microorganisms. Lactose is used slowly. Ammonia is liberated into the
medium resulting into the rise in pH.
Second phase-
There was intense synthesis of penicillin in this phase, due to rapidconsumption of lactose and ammonia
nitrogen. The mycelia mass increases, the pH remainunchanged.
Third phase-
The concentration of antibiotic decreases in the medium. The autolysis of mycelium starts, liberation of
ammonia and slight rise in pH.
33. Kinetic Models
◦ The original model has been extended by including additional input variables such as agitation power and
aeration rate [12].
34. Initial conditions and kinetic parameters.
Table 4:Original fermentation Kinetic model and its initial conditions [12].
35. Figure 9: Glucose and penicillin concentrations at initial glucose concentrations of 15, 25, 30 g/l [12].
36. Step 7: Recovery
1. Filtration.
The penicillin-rich filtrate is cooled to 2–4ºC to avoid chemical or
enzymatic degradation of the penicillin.Filtration is usually achieved by using high-
capacity, rotary vacuum drum filters for separation of the mycelia. The mycelia are
washed on the filter and disposed.
2. Extraction.
◦ solvent extraction is accomplished at low pH such as 2.5–3, using amyl acetate
as solvent.
37. ◦ Continuous, countercurrent, multistage centrifugal extractors are used for this purpose. To avoid
degradation of penicillin during solvent extraction at low pH, temperature is kept around 2–4°C and
filtration time is kept very short (1–2 min).
◦ Two extractors used in series result in nearly 99% penicillin recovery.
38. Step 8:Purification
1. Adsorption.
◦ Carbon adsorption is used to remove impurities and pigments from penicillin-rich
solvent after extraction. Several activated carbon columns in series can be used for
this purpose.
2. Crystallization.
◦ Na and penicillin concentrations, pH, and temperature need to be adjusted for
crystallization.
◦ Excess amounts of Na are added to the penicillin-rich solvent before
crystallization in an agitated vessel. The crystals are separated by a rotary vacuum
filter.
39. ◦ The crystals are washed and predried with anhydrous butyl alcohol to remove some
impurities. Large horizontal belt filters are used for collection and drying of the crystals.
42. References
[1] Waksman, S.A. and Woodruff, H.B., 1940. The soil as a source of microorganisms antagonistic to disease-
producing bacteria. Journal of bacteriology, 40(4), p.581.
[2] Levy, S.B., 1998. The challenge of antibiotic resistance. Scientific American, 278(3), pp.46-53.
[3]Bennett, J.W. and Chung, K.T., 2001. Alexander Fleming and the discovery of penicillin.
[4]Elander, R.P., 2003. Industrial production of β-lactam antibiotics. Applied microbiology and
biotechnology, 61(5-6), pp.385-392.
[5]"inoculum." A Dictionary of Biology. . Encyclopedia.com. 7 Dec. 2018 <https://www.encyclopedia.com>.
[6] Patnaik, P.R., 2001. Penicillin fermentation: mechanisms and models for industrial-scale bioreactors. Critical
reviews in microbiology, 27(1), pp.25-39.
[7] http://www.biologydiscussion.com/fungi/life-cycle-of-penicillium-with-diagram-fungi/63497, accessed
09/12/2018.
43. [8] Meyer, H.P., Minas, W. and Schmidhalter, D., 2017. Industrial-scale fermentation. Industrial Biotechnology: Products
and Processes, pp.1-53.
[9]Foster, J.W., Woodruff, H.B., Perlman, D., McDaniel, L.E., Wilker, B.L. and Hendlin, D., 1946. Microbiological Aspects
of Penicillin: IX. Cottonseed Meal as a Substitute for Corn Steep Liquor in Penicillin Production. Journal of
bacteriology, 51(6), p.695.
[10]Soltero, F.V. and Johnson, M.J., 1953. The effect of the carbohydrate nutrition on penicillin production by Penicillium
chrysogenum Q-176. Applied microbiology, 1(1), p.52.
[11]Holmes, W., Smith, R. and Bill, R., 2006. Evaluation of antifoams in the expression of a recombinant FC fusion
protein in shake flask cultures of Saccharomyces cerevisiae & Pichia pastoris. Microbial Cell Factories, 5(1), p.P30
[12] Bajpai, R.K. and Reuss, M., 1980. A mechanistic model for penicillin production. Journal of Chemical Technology and
Biotechnology, 30(1), pp.332-344.
[13]Varley, J., Brown, A.K., Boyd, J.W.R., Dodd, P.W. and Gallagher, S., 2004. Dynamic multi-point measurement of foam
behaviour for a continuous fermentation over a range of key process variables. Biochemical engineering journal, 20(1),
pp.61-72.
[14]Hillenga, D.J., Versantvoort, H., van der Molen, S., Driessen, A. and Konings, W.N., 1995. Penicillium chrysogenum
takes up the penicillin G precursor phenylacetic acid by passive diffusion. Applied and environmental microbiology, 61(7),
pp.2589-2595.
[15]Deindoerfer, F.H., 1957. Calculation of heat sterilization times for fermentation media. Applied microbiology, 5(4),
p.221.
[16] Moore, D., Robson, G.D. and Trinci, A.P., 2011. 21st century guidebook to fungi with CD. Cambridge University Press.
Editor's Notes
[1] Waksman, S.A. and Woodruff, H.B., 1940. The soil as a source of microorganisms antagonistic to disease-producing bacteria. Journal of bacteriology, 40(4), p.581.
[2] Levy, S.B., 1998. The challenge of antibiotic resistance. Scientific American, 278(3), pp.46-53.
[3]Bennett, J.W. and Chung, K.T., 2001. Alexander Fleming and the discovery of penicillin.
[4]Elander, R.P., 2003. Industrial production of β-lactam antibiotics. Applied microbiology and biotechnology, 61(5-6), pp.385-392.
The natural penicillins have been structurally modified in the laboratory to enhance their efficacy.
These are said to be semisynthetic and were developed to add mainly three properties lacking in penicillin G.
These properties are:
(i) Resistance to β-lactamase (penicillinase),
(ii) Ability to remain active in acidic pH, and
(iii) To enlarge the antibiotic spectrum.
Thiazolidine is a heterocyclic organic compound with the formula (CH2)3S. It is a 5-membered saturated ring with a thioether group and an amine group in the 1 and 3 positions. It is a sulfur analog of oxazolidine. Thiazolidine is a colorless liquid.
Lyophilization (also known as Freeze-drying) is a dehydration process typically used to preserve material or make the material more convenient for transport.
Freeze-drying works by freezing the material and then reducing the surrounding pressure to allow the frozen water in the material to sublime directly from the solid phase to the gas phase.
FREEZE - The product is completely frozen, usually in a vial, flask or tray.
VACUUM - The product is then placed under a deep vacuum, well below the triple point of water.
DRY – Heat energy is then added to the product causing the ice to sublime.
[5]"inoculum." A Dictionary of Biology. . Encyclopedia.com. 7 Dec. 2018 <https://www.encyclopedia.com>.
[6] Patnaik, P.R., 2001. Penicillin fermentation: mechanisms and models for industrial-scale bioreactors. Critical reviews in microbiology, 27(1), pp.25-39.
The term "phenotype" refers to the observable physical properties of an organism; these include the organism's appearance, development, and behavior. An organism's phenotype is determined by its genotype, which is the set of genes the organism carries, as well as by environmental influences upon these genes. Due to the influence of environmental factors, organisms with identical genotypes, such as identical twins, ultimately express nonidentical phenotypes because each organism encounters unique environmental influences as it develops.
[8] Meyer, H.P., Minas, W. and Schmidhalter, D., 2017. Industrial-scale fermentation. Industrial Biotechnology: Products and Processes, pp.1-53.
Titer: the concentration of a solution as determined by titration.
Corn steep liquor is a by-product of corn wet-milling. A viscous concentrate of corn solubles which contains amino acids, vitamins and minerals, it is an important constituent of some growth media. It was used in the culturing of Penicillium during research into penicillin by American microbiologist Andrew J. Moyer.It is an excellent source of organic nitrogen.
[9]Foster, J.W., Woodruff, H.B., Perlman, D., McDaniel, L.E., Wilker, B.L. and Hendlin, D., 1946. Microbiological Aspects of Penicillin: IX. Cottonseed Meal as a Substitute for Corn Steep Liquor in Penicillin Production. Journal of bacteriology, 51(6), p.695.
[10]Soltero, F.V. and Johnson, M.J., 1953. The effect of the carbohydrate nutrition on penicillin production by Penicillium chrysogenum Q-176. Applied microbiology, 1(1), p.52.
[11]Holmes, W., Smith, R. and Bill, R., 2006. Evaluation of antifoams in the expression of a recombinant FC fusion protein in shake flask cultures of Saccharomyces cerevisiae & Pichia pastoris. Microbial Cell Factories, 5(1), p.P30.
[12]Varley, J., Brown, A.K., Boyd, J.W.R., Dodd, P.W. and Gallagher, S., 2004. Dynamic multi-point measurement of foam behaviour for a continuous fermentation over a range of key process variables. Biochemical engineering journal, 20(1), pp.61-72.
[13]Hillenga, D.J., Versantvoort, H., van der Molen, S., Driessen, A. and Konings, W.N., 1995. Penicillium chrysogenum takes up the penicillin G precursor phenylacetic acid by passive diffusion. Applied and environmental microbiology, 61(7), pp.2589-2595.
[14]Deindoerfer, F.H., 1957. Calculation of heat sterilization times for fermentation media. Applied microbiology, 5(4), p.221.