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STATE-OF-THE ART AND DEVELOPMENT PROSPECTS
OF BIOTECHNOLOGICAL INDUSTRY IN REPUBLIC
OF BELARUS
General director of State Research and Production Association “Chemical synthesis and
biotechnologies” – Director of Institute of Microbiology, NAS Belarus
Corresp. member of NAS Belarus Dr. E.I.Kolomiets
By expert estimates global demand of
biotechnological products will reach the value of
2 trillion US dollars, while individual market
segments will tend to expand annually
from 5-7% to 30 %
35% 50% 80%
0%
20%
40%
60%
80%
100%
Chemicals Agricultural products Pharmaceuticals
Biotechnologicalproduce
Products derivedby conventionalmethods
The forecast of Organization for Economic Development and
Cooperation (OEDC) predicts that in 2030 this economic sector will
account for about 3% of GDP in the developed countries, with gradual
substitution of biotechnologies for conventional industrial processes:
«…Science shapes the future of our economy in all
directions… I presume that today Academy of
Sciences is capable to carry out intense
development of space exploration projects, nano-
and bioindustry, robot engineering.»
(А.G.Lukashenko. The annual address to Belarusian
people and National Assembly, 2016)
MAIN OBJECTIVES OF ECONOMIC POLICY IN
BELARUS:
• growth of national competitive potential,
• enlarging the shape of local enterprises at the domestic and foreign markets,
• increasing production efficiency by introducing science-oriented, resource-saving technologies and advanced services
Progress of
biotechnology
acquires
key significance!
YEAR OF SCIENCE
2017
SCIENTIFIC SUPERVISION OF THE DEVELOPMENT OF
BIOTECHNOLOGICAL INDUSTRY IS REALIZED WITHIN
THE FRAMEWORK OF THE PROGRAMS:
State research program “Biotechnologies”
State program “Science-saturated technologies and devices”
(Subprogram1 «Innovative biotechnologies-2020» )
State research-technological program “Industrial bio-and nanotechnologies”
Total volume of funds allocated from state
budget in 2017 – 12,2 mln roubles
Microbial preparations and biotechnologies for
agriculture, diverse industries, medicine,
environmental protection.
The Association makes a massive research
and production cluster controlling various aspects
of bio- and chemical technologies, starting from
elaboration to commercialization of high-tech products and services
Herbicides, fungicides,
disinfecting
agents
DNA technologies for agriculture, medicine, sports, environmental
protection Technologies of production and
application of stem cells, novel antitumor
drugs
The volume of manufactured
biotechnological products, mln BY
roubles
2011
29,2
2016
55,9
Kits for radioimmune,
immunoenzymatic,
immunofluorescent
and other medical
microanalyses
Immunochemical and molecular-
biological diagnostic tools for medicine
and veterinary science
Pharmaceutical
substances and
medicines
Ethanol, fodder
yeasts, carbon
dioxide,
biopreservatives,,
probiotics
Whole and dry milk substitutes, composite fodder concentrates,
premixes, feed additives
THE NATIONAL ACADEMY OF SCIENCES OF BELARUS
SRPA «Chemical synthesis and biotechnologies» (further on – Association)
comprises 10 legal bodies, including 4 research institutions and 6 research and production entities coordinates and monitors development of biotechnological sector in Belarus implements state policy in the area of industrial biotechnology
DATA OF MONITORING PROGRESS OF
BIOTECHNOLOGICAL INDUSTRY IN
BELARUS REPUBLIC
DURING 2012-2016
Market cost of manufactured biotechnological produce
3 bln $
Output of biotechnological products per capita 64,7 $
USA 227 $
EEC 157 $
China 9,7 $
GREEN
BIOTECHNOLOGY
BIOPESTICIDES, MICROBIAL FERTILIZERS
for biological control of diseases and stimulation of
growth in plant species
130 t/yr
16 mln doses/yr
VACCINES for farm animals
PROBIOTICS,PROBIOTIC RATION SUPPLEMENTS for farm stock and poultry
BIOCONSERVATING AGENTS
for ensiling vegetative materials
209 t/yr
257 t/yr
519 thousand t/yr
50 g/yr
ANTITUMOR DRUGS based on chemical-enzymatic
synthesis
CONTRIBUTION OF BIOTECHNOLOGY TO VARIOUS BRANCHES OF ECONOMY
RED BIOTECHNOLOGY
17 500 pcs/yr
DIAGNOSTIC TEST-SYSTEMS
for medicine
760 mln cells/yr
STEM CELL- BASED TECHNOLOGIES
used in regenerative medicine
6986 thousand dal/yr
11 t/yr
33 thousand analyses/yr
DNA DIAGNOSTICS of genetic disease
predisposition
DETECTION OF GENETICALLY MODIFIED ORGANISMS, MARKER-ASSOCIATED BREEDING
AND CERTIFICATION of plants and animals
5600 analyses/yr
WHITE BIOTECHNOLOGY
MICROBIAL
BIOTECHNOLOGIES
ENERGETICS
biofuel:
Butanol,
ethanol,
biodiesel,
biogas, etc.
MEDICINE
substances for
pharmaceuticals,
biopharmaceutic
technologies
AGRICULTURE
plant biocontrol agents,
microbial fertilizers,
probiotics, feed protein,
aminoacids, enzymes, etc.
FOOD INDUSTRY
yeasts, enzymes,
sweeteners, food
additives, ferments,
functional foodstuffs
and nutriceuticals
PETROCHEMISTRY,
MINING OF FOSSILS
reagents, biopolymers, oil extraction aids, preparations for
biogeotechnology
ECOLOGY
biodegraders of
pollutants,
biosensors for
environmental
monitoring
Coordinates activities of
SRPA “Chemical synthesis and
biotechnologies”
Institute of
Microbiology,
NAS Belarus
Monitors implementation of
Plan outlining development of
biotechnological industry in
Belarus for years 2012-2015 and its
extension until 2020
Acts as co-founder from
Belarus republic of Eurasian
technological platform
“Eurasia Bia”
Assigned as principal
contractor of diverse state
research programs in the
sphere of biotechnology
Represents Belarus in East
Palearctic Section of International Organization for
Control of Noxious Species
is the leading research center of
Belarus republic in the area of
microbiology and biotechnology,
including studies on functioning of
cell genome, proteins, intracellular
organelles, individual cells and
investigation of problems related to
nanobiology, like design of
biosensors
Bank
of industrially valuable
microorganisms
(185 strains)
DNA bank
of industrially valuable
microorganisms
(90 specimens)
micromycetes- agents responsible for biodeterioration
of construction materials
(40 strains)
phytopathogenic microorganisms
(100 strains)
microorganisms-degraders
of xenobiotics
(65 strains)
BELARUSIAN COLLECTION OF NON-PATHOGENIC MICROORGANISMS
Specialized collections
Major collection
stock
Incorporates over 2000 microbial strains representing diverse
taxonomic groups. 390 of them are included into specialized depositories:
Belarusian collection was registered by World Federation of Culture Collections (WFCC)
THE NATIONAL ACADEMY OF SCIENCES OF BELARUS
Institute of Microbiology of NAS of Belarus
The tasks:
Center of analytical and genetic engineering research (CAGER)
Molecular-genetic diagnostics of native microorganisms potentially engaged in biotechnological processes
Investigation of bioactive metabolites produced by microbial strains
Search for genetic determinants governing synthesis of bioactive compounds. Engineering of vector systems for molecular cloning
Construction of recombinant strains – hyperproducers of bioactive substances C
AG
ER
is e
qu
ipp
ed
wit
h u
p-t
o-
da
te i
nstr
um
en
ts,
inclu
din
g:
DNA sequencer
DNA amplifier with real-time detection of results
The system for horizontal and vertical phoresis with blotting module
nanospectrophotometer
electroporation unit
water ultrapurification system
chromatographs (gas and high performance liguid with mass-selective detector )
The design pilot plant production capacity estimated for liquid bioproducts
is approximately 30 t per year
Currently Biotechnological Center has arranged output of
over 50 brands of commercial biopreparations
Modernized biological pilot plant (Biotechnological center)
• development and scale-up of original fermentation processes for microbial strains producing biologically valuable substances;
• elaboration of competitive commodity forms for manufactured products
THE NATIONAL ACADEMY OF SCIENCES OF BELARUS
Institute of Microbiology
Pilot-plant unit specializing in recovery, purification and freeze-drying of human lactoferrin derived from
goat milk was launched in 2016
14
Pilot-plant production of enzymes for chemical-enzymatic synthesis of pharmaceutical substances
and formulation of novel diagnostic kits
A unique full-cycle manufacturing plant with the annual capacity of 45 mln activity units allows to meet 100% demand of Belarusian market for enzymes of nucleic acid metabolism
and oxidoreductases used in pharmaceutics and clinical diagnostics
Research and production biotechnological center manufacturing dry commercial forms of biological
preparations will be put into operation in December 2017
Probiotics for prevention and treatment of gastrointestinal diseases, therapy of purulent necrotic skin lesions, for raising productivity and immunobiological status of farm stock, poultry and fish - Bilavet®, Bilavet-С,Bactomast, Synvet®, DКМ®, DКМ-С, Bacinyl-К, Vetosporin, Emilin, Biovir
Probiotic component for whole milk substitute - Lyobact
Feed additives: •probiotic - Sporobact®, Sporobact-К, Proxyferon •enzymatic - Incrifos, Compliferm •based on fungi Pleurotus ostreatus, Cordyceps militaris and yeast Cryptococcus flavescens – Mycorm Plus, Cordycehol, CryptoLife®, CryptoLife-С
Bioconservating agents to ensile plant materials - Lacsil®, Lacsil-МС
Disinfectant for stock and poultry farms - Enatin®
In the years 2006-2016 the researchers of Institute of Microbiology successfully developed and commercialized 23 original import-substituting eco-friendly technologies of producing probiotic
preparations showing antimicrobial, enzymatic, immune-stimulating, antioxidant activities
•ensures decline of fish internal contamination with pathogenic microorganisms from 80-100% to trace levels;
•enhances native (non-specific) resistance of carp organism;
•Emilin application as feed ingredient reduces incidence of carp diseases, raises fish vitality (post-winter survival rate reaches 97%), increases fish weight by 10%
BIOPREPARATIONS FOR COMMERCIAL FISH FARMS
www.mbio.bas-net.by NATIONAL ACADEMY OF SCIENCES, BELARUS, INSTITUTE OF MICROBIOLOGY
BIOPREPARATIONS FOR COMMERCIAL FISH FARMS
• reduces the content of mineral phosphorus, ammonium and nitrate nitrogen twice, blue-green algae population 5-7 fold, phytoplankton thrice;
•Biovir accelerates decay of organic pollutants (estimated in BOD levels) by 1,5 times as compared to the control ponds
www.mbio.bas-net.by NATIONAL ACADEMY OF SCIENCES, BELARUS, INSTITUTE OF MICROBIOLOGY
MICROBIAL DISINFECTANT ENATIN
Active ingredients of disinfectant – cells, spores and antimicrobial metabolites of bacteria Bacillus pumilus
1 2 3 4
Antagonistic activity of Bacillus pumilus BIM В-263 against pathogenic and opportunistic bacteria 1 - Escherichia coli S-3, 2 - Escherichia coli 018, 3 - Staphylococcus sp. , 4 - Streptococcus sp.
EFFICIENCY
Reduction of sanitary-indicative microbiota (Escherichia coli, staphylococcal-streptococcal group):
in air of test sections by 85-53% and 94-43%, respectively;
on the floor and wall surface by 95-81% and 97-63 %, respectively
Intended for sanitation of pig sty complexes and prevention of
contagious diseases in farm animals
The contract worth 85 thousand US
dollars implemented in collaboration
with Institute of Biology, Shandong
Academy of Sciences, China was
focused on development of
technology for manufacturing
microbiocide
INMI-bactodez –Enatin analog for
prophylactic disinfection of stock
and poultry farms
Over 153 t of ecologically safe probiotics manufactured and marketed during 2015-2016 ensured output of prime quality farm products free of antibiotics and therapeutic chemicals,
with overall economic effect exceeding 5 mln $
Feeding trials demonstrated that probiotics and probiotic ration supplements developed at the
Institute promoted:
45-50 % shortening of pathological cycle in farm
animals
6-10 % increase of live
bodyweight gains
reduction of unit fodder expense per 1 kg of mass increment by 12
– 18 %
improved quality of farm
products
The capacity of world
biopesticide market
reaches 67,5 bln. dollars.
The average annual
uprise of this market
constitutes 6,2%
PLANT BIOLOGICAL CONTROL AGENTS –
AS AN ALTERNATIVE TO AGROCHEMICALS
Current leaders of global biopesticide market -
corporations BASF, Bayer CorpScience, Singenta
have spurred up commodity sales to 3 bln US
dollars
Virtually all huge companies specializing
in research and development of
biocontrol preparations are boosting pesticide fabrication to derive
profit from upsurge in product demand
To date laboratory technologies have been
developed and scaled up to industrial level at
Institute of Microbiology, NAS Belarud for
14 innovative biopreparations distinguished by
phytoprotective activity, high efficiency and
awarded medals and trophies at international
exhibitions.
5,7 7,9
28,3
132,7
25,1
120,4
0
20
40
60
80
100
120
140ton
FABRICATION OF BIOPESTICIDES AND COMPLEX
MICROBIAL PREPARATIONS
Export amount
Based on bacteria with antagonistic,
cellulolytic, phosphate-mobilizing and nitrogen-
fixing activities:
Complex biopreparation
POLYBACT For recovery of soil
microbial cenosis and promotion of crop
productivity,
acting according to
SIX-IN-ONE principle
Suppresses development of pathogenic microflora and provides for restoration of agrobiocenoses
1
2
3
4
5
6
Accelerates decomposition of plant residues in soil
Carries out mobilization of insoluble phosphor-containing compounds
Enriches soil with biological nitrogen
Increases productivity of cultivars by 10-20%
Raises soil fertility
CONTROL CONTROL
CONTROL CONTROL
CONTROL
CONTROL
EXPERIMENT EXPERIMENT
EXPERIMENT EXPERIMENT EXPERIMENT
EXPERIMENT
www.mbio.bas-net.by NATIONAL ACADEMY OF SCIENCES, BELARUS, INSTITUTE OF MICROBIOLOGY
• Reduces the level of residual
herbicides of sulfonylurea and
imidosalinone series in soil by
10-26%
• Suppresses development of
pathogenic microbiota and
secures recovery of
agrobiocenoses
• Raises efficiency of herbicide
action by 15-30 % and retards
their inhibiting effect on
cultivars
• Increases seed germination
rate by 15-25 %, promotes
crop harvests by 12-17 %
COMPLEX MICROBIAL PREPARATION
AGROREVITOL
Chromatogram of cultural medium with
chlorimuron-ethyl(100 MPC)
Phytotoxicity of liquid medium containing herbicide
imazamox (50 MPC) without biopreparation (а) and
in its presence(b)
а б
experiment
control
complex biopreparation for biological control of vegetable crop diseases in open fields;
for biological control of vegetable crop diseases in open fields
upgrades quality of vegetables and increases harvests by over 10%;
biological efficiency against angular leaf spot of cucumbers exceeds 55%
COMPLEX BIOPREPARATION
www.mbio.bas-net.by NATIONAL ACADEMY OF SCIENCES, BELARUS, INSTITUTE OF MICROBIOLOGY
Molecular-genetic characterization of microbial associations in mixed biocenoses (metagenomic studies); bioregulation of plant-microbial interaction; control of gastrointestinal microbiocenoses in farm stock, poultry, fish and humans to reduce risks of disease infection and progression.
INNESTIGATION TRENDS IN THE AREA OF MICROBIAL
BIOTECHNOLOGIES
Upgrading available microbial resources using genetic engineering approaches to select hyperproductive strains distinguished by phage resistance and enhanced adaptability to diverse biotic conditions for biotechnological processes
Development of novel efficient biotechnologies for fabrication of diverse biological preparations by targeted control of microbial activity, of fermentation processes and commercial optimization forms of the products
Preservation of
human health
hinges on the
formation and
maintenance of
normal microbial
ecosystem
METAGENOMIC STUDIES OF HUMAN
SYMBIOTIC MICROFLORA
- special «metabolic organ», responsible for a
broad spectrum of vital local and systemic
functions
• Causes essential influence on structural-functional state of internal organs and immune system,
• Promotes harmonic relationship of macrohost with exogenous microbial environment;
HUMAN MICROBIOTA
- weights about 2 kg and contains approximately
10 ¹⁴ microbial cells, exceeding 10 times the
number of human cells. The quantity of microbial genes is 150-360 times higher than the amount of genes in human genome;
- any biochemical process or significant function
in the human body directly or indirectly involves
symbiotic microorganisms
Metagenomics turned into a critical tool for
elucidation of correlations between microbiota
and human pathologies, allowing to investigate in
detail association of some microbial taxa and
functional gene clusters with clinical status of
the patients
Studies planned within the framework of joint collaboration
project with the National Research and Practical Center of
Kid Oncology, Hematology and Immunology:
Metagenomic analysis of intestinal
microbiota in children suffering
from cancer diseases before
and after transplanting
hemapoietic stem cells
Recovery dynamics of gut
microbiocenosis in post-
transplantation period
Identification of microbial taxa
related to «pathological process and
determination of host-transplant
response»
Development of methods to prevent post-transplanting
complications
•Uridinephosphorylases
•Thymidinephosphorylases
•Purinenucleosidephophorylases
for elaboration and industrial scale-up of technologies aimed at producing active substances for antitumor
drugs Leucladin and Fludarabel
Genetically modified strains hyperproducing pharmacologically valuable ENZYMES OF NUCLEIC ACID METABOLISM WERE ENGINEERED:
They laid the basis:
According to the data of ChemPharmSynthesis research-production center, economy of hard currency caused by local market supplies of
manufactured batches of Leucladin and Fludarabel in the latest decade (2006-2016) totaled over 2,5 mln US dollars.
APPLICATION
• Highly active strains-producers of glucose oxidase - fungi Penicillium were isolated and transformed using genetic engineering methods
• Pilot-plant technology for producing glucose oxidase preparation was elaborated
• Glucose oxidase was manufactured and used in fabrication of 3,8 bln amperometric biosensors «Glucosen» in year prescribed for diabetes patients
Biosensors technology for express-analysis of glucose and analytical
control of biotechnological process
Food industry as a preservative
Medicine for glucose blood tests
and as external therapeutic agent
Chemical industry for production of gluconic
acid, gluconate and hydroquinone
www.mbio.bas-net.by NATIONAL ACADEMY OF SCIENCES, BELARUS, INSTITUTE OF MICROBIOLOGY
EXPORT of drugs fabricated in Belarus constituted 115 mln US dollars (12% rise in comparison with 2015) and the commodities were shipped to 29 countries.
65%
35%
2013 г. Importedmedicines
Local pharmaproducts
The monetary capacity of pharmaceutical market in Belarus was estimated to reach 636,8 mln US dollars by the end of 2016
The shape of Belarusian drugs at the domestic market
48% 52%
2016 г.
According to the recent update (March 1, 2017), the overall Belarusian register comprised 4 500 medicines, including 1 600 home-made entries
Society of Russian biotechnologists, Moscow, Russia
Institute of Microbiology, NAS Belarus, Minsk, Belarus
National Center of Biotechnologies, Science Committee, Ministry of Science and Education of Kazakhstan
republic, Astana,Kazakhstan
Development of biotechnology to meet the interests of science, education, economic sector, social sphere, state system
Formation and perfection of Eurasian biotechnological infrastructure
Elaboration and commercialization of novel biotechnologies, joint implementation of projects within the tramework of the program «Bioeconomic strategy for Eurasia»
Engineering communication retwork and promoting international scientific-technological cooperation
THE FOUNDERS:
The objectives:
The platform was approved by the decision of Eurasian Intergovernmental Council № 2 or April 13, 2016
Interstate cooperation within the framework of Eurasian technological platform
«EurasiaBio», uniting 37 institutions, including 37 entities from Russia,16 – from
Belarus, 8 from Kazakhstan
Development prospects of biotechnological industry:
Production zones
Location:
Academic hub, Minsk
are formed in Belarus based on exterritorial
principle
By October 25, 2016 30 innovation or invertment projects
were selected for realization under the acgis of BelBiograd
initiative with overall funding 176 mln Belarusian roubles
Development prospects of biotechnological industry:
KEY BELBIOGRAD PROJECTS IN
THE FIELD OF BIOTECHNOLOGY:
• Construction of probiotic production plant for agrarian sector of Belarus republic with annual design capacity 250 ton of dry biopreparations (projects coordinators – company Biocom Ltd and Institute of Microbiology, NAS Belarus)
• Manufacturing of genetic and innovative pharmaceutical veterinary preparations with total output of 4 ml units per year (the contractor – research-production center BelAgroGen)
• Design and construction of mining and chemical processing combine specializing in thermobiochemical transformation of peat with estimated annual production of 150 thousand tons of humic preparations (assigned to Institute of Natural Resource Management, NAS Belarus and state manufacturing concern Beltopgas)
THE ESTIMATED COST of biotechnological produce manufactured in Belarus
will equal 1.08 bln Belarusian roubles by 2020
0,41 bln rbl.
1,08 bln rbl.
2011
2020 (forecast)
2015 0,73 bln rbl.
TO ACCELERATE DEVELOPMENT OF
BIOECONOMIC SECTOR WILL:
intensify substitution of local analogs for imported commodities
raise competitive ability of generated products at the global market
PROPOSALS FOR COOPERATION PARTNERS:
Concluding contracts to generate new types of scientific-technological products
Signing license agreements to transfer technologu application rights
Initiating joint enterprises and venture projects
Advisory assistance in mastering new biotechnologies
Training of highly skilled professionals at the premises of Institute of Microbiology, NAS Belarus
Thank you for attention!
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