Editing Corynebacterium (section)

==Industrial uses==
Nonpathogenic species of ''Corynebacterium'' are used for important industrial applications, such as the production of [[amino acid]]s<ref>{{cite book |editor1-last=Yamada |editor1-first=K. |editor2-last=Kinoshita |editor2-first=S. |editor3-last=Tsunoda |editor3-first=T. |editor4-last=Aida |editor4-first=K. |year=1972 |title=The Microbial Production of Amino Acids |publisher=Wiley |location=New York }}</ref> and [[nucleotide]]s, bioconversion of [[steroid]]s,<ref>{{cite journal |doi=10.1002/bit.260220110 |pmid=7350926 |title=Steroid transformation at high substrate concentrations using immobilized ''Corynebacterium'' simplex cells |journal=Biotechnology and Bioengineering |volume=22 |issue=1 |pages=119–36 |year=1980 |last1=Constantinides |first1=Alkis |s2cid=29703826 }}</ref> degradation of [[hydrocarbon]]s,<ref>{{cite journal |pmid=422512 |pmc=218359 |year=1979 |last1=Cooper |first1=D. G. |title=Analysis of corynomycolic acids and other fatty acids produced by Corynebacterium lepus grown on kerosene |journal=Journal of Bacteriology |volume=137 |issue=2 |pages=795–801 |last2=Zajic |first2=J. E. |last3=Gracey |first3=D. E. |doi=10.1128/JB.137.2.795-801.1979 }}</ref> [[cheese]] aging,<ref>{{cite journal |doi=10.1111/j.1574-6968.1985.tb01591.x |title=Phenylalanine and tyrosine catabolism in some cheese coryneform bacteria |journal=FEMS Microbiology Letters |volume=26 |issue=2 |pages=201–5 |year=1985 |last1=Lee |first1=Chang-Won |last2=Lucas |first2=Serge |last3=Desmazeaud |first3=Michel J. |doi-access=free }}</ref> and production of [[enzyme]]s.<ref>{{cite journal |doi=10.1002/(SICI)1097-0134(20000401)39:1<68::AID-PROT7>3.0.CO;2-Y |pmid=10737928 |title=Molecular modeling of substrate binding in wild-type and mutant ''Corynebacteria'' 2,5-diketo-D-gluconate reductases |journal=Proteins: Structure, Function, and Genetics |volume=39 |issue=1 |pages=68–75 |year=2000 |last1=Khurana |first1=Sumit |last2=Sanli |first2=Gulsah |last3=Powers |first3=David B. |last4=Anderson |first4=Stephen |last5=Blaber |first5=Michael |display-authors=3|citeseerx=10.1.1.661.3412 |s2cid=24526523 }}</ref> Some species produce metabolites similar to [[antibiotic]]s: [[bacteriocin]]s of the corynecin-linocin type,<ref name=jk /><ref>{{cite journal |doi=10.1111/j.1574-6968.1984.tb01451.x |title=Plasmid-associated bacteriocin production in a JK-type coryneform bacterium |journal=FEMS Microbiology Letters |volume=25 |issue=2–3 |pages=179–82 |year=1984 |last1=Kerry-Williams |first1=S.M. |last2=Noble |first2=W.C. |doi-access=free }}</ref><ref>{{cite journal |doi=10.1271/bbb1961.36.2223 |title=Production of Antibacterial Compounds Analogous to Chloramphenicol by a n-Paraffin-grown Bacterium |journal=Agricultural and Biological Chemistry |volume=36 |issue=12 |pages=2223–8 |year=1972 |last1=Suzuki |first1=Takeo |last2=Honda |first2=Haruo |last3=Katsumata |first3=Ryoichi |doi-access=free }}</ref> antitumor agents,<ref>{{cite book |doi=10.1016/S0065-230X(08)60090-1 |pmid=343523 |chapter=Antitumor Activity of Corynebacterium Parvum |volume=26 |pages=257–306 |year=1978 |last1=Milas |first1=Luka |last2=Scott |first2=Martin T. |isbn=978-0-12-809878-3 |editor1-first=Marvella E. |editor1-last=Ford |editor2-first=Dennis K. |editor2-last=Watson |series=Advances in Cancer Research | title = Cancer Disparities | edition = 1st}}</ref> etc. One of the most studied species is [[Corynebacterium glutamicum|''C. glutamicum'']], whose name refers to its capacity to produce [[glutamic acid]] in aerobic conditions.<ref>{{cite journal |doi=10.2323/jgam.13.279 |title=Taxonomical Studies on Glutamic Acid-Producing Bacteria |journal=The Journal of General and Applied Microbiology |volume=13 |issue=3 |pages=279–301 |year=1967 |last1=Abe |first1=Shigeo |last2=Takayama |first2=KEN-Ichiro |last3=Kinoshita |first3=Shukuo |doi-access=free }}</ref>

L-Lysine production is specific to ''C. glutamicum'' in which core metabolic enzymes are manipulated through genetic engineering to drive metabolic flux towards the production of NADPH from the pentose phosphate pathway, and L-4-aspartyl phosphate, the commitment step to the synthesis of L-lysine, [[lysC]], {{chem name|dapA}}, {{chem name|dapC}}, and {{chem name|dapF}}. These enzymes are up-regulated in industry through genetic engineering to ensure adequate amounts of lysine precursors are produced to increase metabolic flux. Unwanted side reactions such as threonine and asparagine production can occur if a buildup of intermediates occurs, so scientists have developed mutant strains of'' C. glutamicum'' through PCR engineering and chemical knockouts to ensure production of side-reaction enzymes are limited. Many genetic manipulations conducted in industry are by traditional cross-over methods or inhibition of transcriptional activators.<ref>{{cite book |last1=Kjeldsen |first1=Kjeld Raunkjær |year=2009 |title=Optimization of an industrial L-lysine producing Corynebacterium glutamicum strain |type=PhD Thesis |publisher=Technical University of Denmark |oclc=826400572 }}{{page needed|date=January 2017}}</ref>

Expression of functionally active human [[epidermal growth factor]] has been brought about in ''C. glutamicum'',<ref>{{cite journal |doi=10.1111/j.1472-765X.2005.01802.x |pmid=16411922 |title=Secretion of human epidermal growth factor by Corynebacterium glutamicum |journal=Letters in Applied Microbiology |volume=42 |issue=1 |pages=66–70 |year=2006 |last1=Date |first1=M. |last2=Itaya |first2=H. |last3=Matsui |first3=H. |last4=Kikuchi |first4=Y. |s2cid=20867427 |doi-access=free }}</ref> thus demonstrating a potential for industrial-scale production of human proteins. Expressed proteins can be targeted for secretion through either the general [[secretory pathway]] or the [[twin-arginine translocation pathway]].<ref>{{cite journal |doi=10.1007/s00253-007-0934-8 |pmid=17453196 |title=Comparative analysis of twin-arginine (Tat)-dependent protein secretion of a heterologous model protein (GFP) in three different Gram-positive bacteria |journal=Applied Microbiology and Biotechnology |volume=76 |issue=3 |pages=633–42 |year=2007 |last1=Meissner |first1=Daniel |last2=Vollstedt |first2=Angela |last3=Van Dijl |first3=Jan Maarten |last4=Freudl |first4=Roland |s2cid=6238466 }}</ref>

Unlike gram-negative bacteria, the gram-positive ''Corynebacterium'' species lack [[lipopolysaccharide]]s that function as antigenic [[endotoxins]] in humans.{{citation needed|date=January 2017}}