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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

STATE-OF-THE ART AND DEVELOPMENT PROSPECTS OF BIOTECHNOLOGICAL … · controlling various aspects of bio- and chemical technologies, starting from elaboration to commercialization

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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!