**Conflict of interest**

and fungi are the major sources of β-lactam antibiotics. The Gram-positive *Streptomyces clavuligerus* is able to produce both clavulanic acid and cephamycin, since the Gram-negative bacterium *Lysobacter lactamgenus* produces cephabacins. Two hypotheses have been put forward for β-lactam biosynthesis: (1) horizontal gene transfer (HGT) from bacteria to fungi and (2) vertical descent (originated from a common ancestor). Bioinformatics, genetic designs,

The production of β-lactam antibiotic occurs through three different steps: prebiosynthetic steps, intermediate formation steps, and late steps (also known as decorating steps) [71–76]. The biosynthesis of building blocks for β-lactam consist of L-α-aminoadipic acid, L-cysteine, and L-valine. L-α-Aminoadipic acid is not a proteinogenic amino acid formed from L-lysine. The actinomycete

The two starting enzyme reactions are omnipresent in fungi and cephalosporin biosynthesis. D-(L-Aminoadipyl)-L-cysteinyl-D-valine synthase is the first enzyme, using all three amino acids gathered into a tripeptide through condensation reaction. This enzyme is NRPS encoded by the acvA (pcbAB) gene. The next step is the synthesis of a bicyclic ring (a four-member β-ring is fused with a five-member thiazolidine ring) through an oxidative reaction, catalyzed by isopencillin N-synthase, and results in the formation of isopenicillin N. Cephalosporin– cephamycin biosynthesis is the development of the five-member thiazolidine ring into a six-member dihydrothiazine ring. Several enzymes consecutively contribute to this ring conversion. β--Lactam biosynthesis is synthesized by a gene, which is usually clustered in the DNA of all reproducing bacteria. Bacterial species capable of producing β--lactam antibiotics exhibit an ecological benefit. In contrast, β-lactam–producing bacteria show low sensitivity to β-lactams on their own, or they have evolved to inactivate β-lactam antibiotics by β-lactamase

*Streptomyces* are able to produce a number of antibiotics and other important pharmaceutical drugs to treat infections caused by bacteria and fungi, cancer, and heart-related diseases. Bacterial species reveal a complex lifecycle with physiological and biochemical adaptability, along with the ability to synthesize a large variety of secondary metabolites, presenting complex structures following different metabolic pathways. Understanding the secondary metabolite biosynthesis and pathways would lead to progress in combinatorial biosynthesis

We thank Miss Susan Ann Hill for technical assistance and for her useful contribution to the

and sequence identity are more beneficial in HGT.

116 Basic Biology and Applications of Actinobacteria

in the pharmaceutical and biotechnology industries.

enzymes.

**4. Conclusion**

**Acknowledgements**

English manuscript checking.

lysine 6-aminotransferase converts L-lysine into L-α-aminoadipic acid.

The authors declare that no conflicting interest exists.
