Can Bacteria Produce Blockbuster Antibacterial: The Penicillin?


Microbes produce a large number of bioactive molecules. Antibiotics are among the most exploited secondary metabolites. Their consistent and invariably indiscriminate usage by human beings to get rid of plant and animal pathogens has resulted in the emergence of multiple drug resistant microbes. At this juncture, the questions being raised are: (i) Shall we endeavour for novel antibiotics, (ii) Search novel antibiotic producers, (iii) Transform presently “non”-producers to producers by genetically modifying the antibiotic production machinery?

The important antibiotics

β-lactams account for more than 60% of the antibiotics used around the world but there are a few organisms which have the ability to produce them in an efficient manner. Generally, filamentous fungi Penicillium chrysogenum is used for producing Penicilllin G (β-lactam). Bacteria and fungi share high homology in the genes involved in the β-lactam biosynthetic pathway. However, this information has not proved effective in improving β-lactam production efficiency.

Biosynthetic pathway

Penicillin synthesis proceeds by the formation of tripeptide (ACV) composed of: L-α-aminoadipyl, L-cysteinyl and D-valine, which is mediated by the enzyme ACV synthetase, which in turn gets cyclised to isopenicillin N, with the aid of isopenicillin N synthase (IPNS). The exchange between the α-aminoadipic lateral chain with phenylacetyl-CoA lead to the production of penicillin G. The genes for the synthesis of this antibiotics:pcbAB encoding for ACV synthetase and pcbC encoding for ACV cyclase, show similarity between fungi (Penicillium notatum, P. chrysogenum, and Aspergillus nidulans) and bacteria (Bacillus peptidase genes).

The antibacterial- Penicillin

Penicillin inhibits the biosynthesis of the peptidoglycan layer i.e. the bacterial cell wall. During its biosynthesis, the final step of transpeptidation is carried out by transpeptidases. β-lactam antibiotics - the analogues of D-alanyl-D-alanine, which are the major amino acid residues of the nascent peptidoglycan layer, which is composed of: (i) N-acetyl glucosamine, and (ii) N-acetyl muramic acid peptide subunits. The binding of β-lactam antibiotics inhibits binding proteins (PBP’s), which in turn inhibits the cross-linking of the peptidoglycan layer. The net result is the disruption of cell wall synthesis.

Can bacteria produce penicillin?

We all know that production of penicillin will be counterproductive for the bacteria.

But, Can bacteria produce this antibiotic?

Comparative genomics approach revealed that Burkholderia fungorum and Mesorhizobium loti are two bacterial species, which have genes involved in the biosynthesis of penicillin and cephalosporin. There are a few other bacteria, which lack only one gene responsible for ACV synthetase: Rhodopseudomonas palustris and Magnetospirillum magnetotacticum. Can these bacteria produce penicillin? In principle, it should be possible to use these bacteria by genetically modifying them, say by introducing the missing gene(s).

Why bacteria cannot produce penicillin?

For penicillin production, the organisms needs a machinery composed of: genes for β-lactam biosynthesis, production of α-aminoadipic acid, antibiotic resistance, and efflux of the final product. M. loti and B. fungorum possess most of potential genes, except for ACV synthase and cmcT, respectively. As a consequence, these bacteria have never been identified as β-lactam producers. This hypothesis finds support from strains of Penicillium crustosum and P. verrucosum, which lack penicillin gene clusters and are among the non-producers of β-lactams.


Genomics and bioinformatics can be exploited as tools to search for novel and potential candidates, which can be transformed from “non”-producers to producers.


1. Agarwala M, Choudhury B, Yadav RNS (2014) Comparative study of antibiofilm activity of copper oxide and iron oxide nanoparticles against multidrug resistant biofilm forming uropathogens. Indian J Microbiol 54:365-368. doi: 10.1007/s12088-014-0462-z
2. Alipiah NM, Shamsudin MN, Yusoff FM, Arshad A (2015) Membrane biosynthesis gene disruption in methicillin-resistant Staphylococcus aureus (MRSA) as potential mechanism for reducing antibiotic resistance. Indian J Microbiol 54:41-49. doi: 10.1007/s12088-014-0488-2
3. Arasu MV, Al-Dhabi NA, Rejiniemon TS, Lee KD, Huxley VAJ, Kim DH, Duraipandiyan V, Karuppiah P, Choi KC (2015) Identification and characterization of Lactobacillus brevis P68 with antifungal, antioxidant and probiotic functional properties. Indian J Microbiol 55:19-28. doi: 10.1007/s12088-014-0495-3
4. Gui Z, Wang H, Ding T, Zhu W, Zhuang X, Chu W (2014) Azithromycin reduces the production of α-hemolysin and biofilm formation in Staphylococcus aureus. Indian J Microbiol 54:114-117. doi: 10.1007/s12088-013-0438-4
5. Hema M, Balasubramanian S, Princy SA (2015) Meddling Vibrio cholerae murmurs: A neoteric advancement in cholera research. Indian J Microbiol 55:121-130. doi:10.1007/s12088-015-0520-1
6. Kalia VC (2014) Microbes, antimicrobials and resistance: The battle goes on. Indian J Microbiol 54:1-2. doi: 10.1007/s12088-013-0443-7
7. Kalia VC (2015) Quorum Sensing vs Quorum Quenching: A Battle with No End in Sight.
8. Kalia VC (2015) Microbes: The most friendly beings? In: Quorum Sensing vs Quorum Quenching: A Battle with No End in Sight, 1-5. Editor: VC Kalia. Springer India. doi:10.1007/978-81-322-1982-8_1
9. Kalia VC, Prakash J, Koul S, Ray S (2016) Simple and rapid method for detecting biofilm forming bacteria. Indian J Microbiol 56:1-3. doi: 10.1007/s12088-016-0616-2
10. Kalia VC, Kumar P (2015) Genome wide search for biomarkers to diagnose Yersinia infections. Indian J Microbiol 55:366-374. doi: 10.1007/s12088-015-0552-6
11. Kalia VC, Kumar P, Kumar R, Mishra A, Koul S (2015) Genome wide analysis for rapid identification of Vibrio species. Indian J Microbiol 55:375-383. doi: 10.1007/s12088-015-0553-5
12. Kalia VC, Kumar P, Pandian SK, Sharma P (2014) Biofouling control by quorum quenching. Hb_25 Springer Handbook of Marine Biotechnology Chapter 15:431-440. Springer Ed. S. K. Kim.
13. Kalia VC, Rani A, Lal S, Cheema S, Raut CP (2007) Combing databases reveals potential antibiotic producers. Expert Opin Drug Discov 2:211-224. doi:10.1517/17460441.2.2.211
14. Kalia VC, Wood TK, Kumar P (2014) Evolution of resistance to quorum-sensing inhibitors. Microb Ecol 68:13-23. doi:10.1007/s00248-013-0316-y
15. Kalia VC, Kumar P (2015) Potential applications of quorum sensing inhibitors in diverse fields. In: Quorum Sensing vs Quorum Quenching: A Battle with No End in Sight, 359-370. Editor: VC Kalia. Springer India. doi:10.1007/978-81-322-1982-8_29
16. Kalia VC, Kumar P (2015) The Battle: Quorum-sensing inhibitors versus evolution of bacterial resistance. In: Quorum Sensing vs Quorum Quenching: A Battle with No End in Sight, 385-391. Editor: VC Kalia. Springer India. doi:10.1007/978-81-322-1982-8_31
17. Kaur G, Rajesh S, Princy SA (2015) Plausible drug targets in the Streptococcus mutans quorum sensing pathways to combat dental biofilms and associated risks. Indian J Microbiol 55:349-357. doi:10.1007/s12088-015-0534-8
18. Koul S, Kumar P, Kalia VC (2015) A unique genome wide approach to search novel markers for rapid identification of bacterial pathogens. J Mol Genet Med 9:194. doi: 10.4172/1747-0862.1000194
19. Koul S, Prakash J, Mishra A, Kalia VC (2016) Potential emergence of multi-quorum sensing inhibitor resistant (MQSIR) bacteria. Indian J Microbiol 56:1-18. doi: 10.1007/s12088-015-0558-0
20. Kumar P, Koul S, Patel SKS, Lee JK, Kalia VC (2015) Heterologous expression of quorum sensing inhibitory genes in diverse organisms. In: Quorum Sensing vs Quorum Quenching: A Battle with No End in Sight, 343-356. Editor: VC Kalia. Springer India. doi:10.1007/978-81-322-1982-8_28
21. Kumar P, Patel SKS, Lee JK, Kalia VC (2013) Extending the limits of Bacillus for novel biotechnological applications. Biotechnol Adv 31:1543-1561. doi:10.1016/j.biotechadv.2013.08.007
22. Laich F, Fierro F, Martin JF (2002) Production of penicillin by fungi growing on food products: Identification of a complete penicillin gene cluster in Penicillium griseofulvum and a truncated cluster in Penicillium verrucosum. Appl Environ Microbiol 68:1211-1219. doi: 10.1128/AEM.68.3.1211-1219.2002
23. Mahale KN, Paranjape PS, Marathe NP, Dhotre DP, Chowdhury S, Shetty SA, Sharma A, Sharma K, Tuteja U, Batra HV, Shouche YS (2014) Draft genome sequences of Yersinia pestis strains from the 1994 plague epidemic of Surat and 2002 Shimla outbreak in India. Indian J Microbiol 54:480-482. doi: 10.1007/s12088-014-0475-7
24. Moroeanu VI, Vamanu E, Paun G, Neagu E, Ungureanu OR, Eremia SAV, Radu GL, Ionescu R, Pelinescu DR (2015) Probiotic strains influence on infant microbiota in the in vitro colonic fermentation model GIS1. Indian J Microbiol 55:423-429. doi: 10.1007/s12088-015-0542-8
25. Prakasham RS, Kumar BS, Kumar YS, Kumar KP (2014) Production and characterization of protein encapsulated silver nanoparticles by marine isolate Streptomyces parvulus SSNP11. Indian J Microbiol 54:329-336. doi: 10.1007/s12088-014-0452-1
26. Purohit HJ, Cheema S, Lal S, Raut CP, Kalia VC (2007) In search of drug targets for Mycobacterium tuberculosis. Infect Disord Drug Targets 7:245-250. doi: 10.2174/187152607782110068
27. Saxena A, Mukherjee M, Kumari R, Singh P, Lal R (2014) Synthetic biology in action: Developing a drug against MDR-TB. Indian J Microbiol 54:369-375. doi:10.1007/s12088-014-0498-0
28. Shang Z, Wang H, Zhou S, Chu W (2014) Characterization of N-acyl-homoserine lactones (AHLs)-deficient clinical isolates of Pseudomonas aeruginosa. Indian J Microbiol 54:158-162. doi: 10.1007/s12088-014-0449-9
29. Wang R, Fang S, Xiang S, Ling S, Yuan J, Wang S (2014) Generation and characterization of a scFv antibody against T3SS needle of Vibrio parahaemolyticus. Indian J Microbiol 54:143-150. doi: 10.1007/s12088-013-0428-6

About Author / Additional Info:
Researcher at Microbial Biotechnology and Genomics at CSIR-IGIB, Delhi.